Therapeutic advances of targeting receptor tyrosine kinases in cancer.

Cohen, S. Isolation of a mouse submaxillary gland protein accelerating incisor eruption and eyelid opening in the new-born animal. J. Biol. Chem. 237, 1555–1562 (1962).

pubmed: 13880319 doi: 10.1016/S0021-9258(19)83739-0

Levi-Montalcini, R. & Booker, B. Excessive growth of the sympathetic ganglia evoked by a protein isolated from mouse salivary glands. Proc. Natl Acad. Sci. USA 46, 373–384 (1960).

pubmed: 16578496 pmcid: 222844 doi: 10.1073/pnas.46.3.373

De Meyts, P., Roth, J., Neville, D. M., Gavin, J. R. & Lesniak, M. A. Insulin interactions with its receptors: experimental evidence for negative cooperativity. Biochem. Biophys. Res. Commun. 55, 154–161 (1973).

pubmed: 4361269 doi: 10.1016/S0006-291X(73)80072-5

Carpenter, G. & Cohen, S. 125I-labeled human epidermal growth factor. Binding, internalization, and degradation in human fibroblasts. J. Cell Biol. 71, 159–171 (1976).

pubmed: 977646 doi: 10.1083/jcb.71.1.159

Ushiro, H. & Cohen, S. Identification of phosphotyrosine as a product of epidermal growth factor-activated protein kinase in A-431 cell membranes. J. Biol. Chem. 255, 8363–8365 (1980).

pubmed: 6157683 doi: 10.1016/S0021-9258(18)43497-7

Kasuga, M., Zick, Y., Blithe, D. L., Crettaz, M. & Kahn, C. R. Insulin stimulates tyrosine phosphorylation of the insulin receptor in a cell-free system. Nature 298, 667–669 (1982).

pubmed: 6178977 doi: 10.1038/298667a0

De Meyts, P. Receptor tyrosine kinase signal transduction and the molecular basis of signalling specificity. in Receptor Tyrosine Kinases: Structure, Functions and Role in Human Disease 51–76 (Springer New York, New York, NY, 2015). https://doi.org/10.1007/978-1-4939-2053-2_4 .

Zhao, M., Jung, Y., Jiang, Z. & Svensson, K. J. Regulation of energy metabolism by receptor tyrosine kinase ligands. Front. Physiol. 11, 1–23 (2020).

doi: 10.3389/fphys.2020.00354

Vaparanta, K. et al. An extracellular receptor tyrosine kinase motif orchestrating intracellular STAT activation. Nat. Commun. 13, 1–19 (2022).

doi: 10.1038/s41467-022-34539-4

Gonzalez-Magaldi, M., McCabe, J. M., Cartwright, H. N., Sun, N. & Leahy, D. J. Conserved roles for receptor tyrosine kinase extracellular regions in regulating receptor and pathway activity. Biochem. J. 477, 4207–4220 (2020).

pubmed: 33043983 doi: 10.1042/BCJ20200702

Yao, Z. & Stagljar, I. Multiple functions of protein phosphatases in receptor tyrosine kinase signaling revealed by interactome analysis. Mol. Cell Oncol. 4, 1–3 (2017).

Grassot, J., Gouy, M., Perrière, G. & Mouchiroud, G. Origin and molecular evolution of receptor tyrosine kinases with immunoglobulin-like domains. Mol. Biol. Evol. 23, 1232–1241 (2006).

pubmed: 16551648 doi: 10.1093/molbev/msk007

Stuttfeld, E. & Ballmer‐Hofer, K. Structure and function of VEGF receptors. IUBMB Life 61, 915–922 (2009).

pubmed: 19658168 doi: 10.1002/iub.234

Diwanji, D., Thaker, T. & Jura, N. More than the sum of the parts: toward full‐length receptor tyrosine kinase structures. IUBMB Life 71, 706–720 (2019).

pubmed: 31046201 pmcid: 6531341 doi: 10.1002/iub.2060

Matsushita, C. et al. Transmembrane helix orientation influences membrane binding of the intracellular juxtamembrane domain in Neu receptor peptides. Proc. Natl Acad. Sci. USA 110, 1646–1651 (2013).

pubmed: 23319611 pmcid: 3562775 doi: 10.1073/pnas.1215207110

Hedger, G., Sansom, M. S. P. & Koldsø, H. The juxtamembrane regions of human receptor tyrosine kinases exhibit conserved interaction sites with anionic lipids. Sci. Rep 5, 1–10 (2015).

doi: 10.1038/srep09198

Lemmon, M. A. & Schlessinger, J. Cell signaling by receptor tyrosine kinases. Cell 141, 1117–1134 (2010).

pubmed: 20602996 pmcid: 2914105 doi: 10.1016/j.cell.2010.06.011

Hafizi, S. & Dahlblack, B. Signalling and functional diversity within the Axl subfamily of receptor tyrosine kinases. Cytokine Growth Factor Rev. 17, 295–304 (2006).

pubmed: 16737840 doi: 10.1016/j.cytogfr.2006.04.004

Aveic, S. & Tonini, G. P. Resistance to receptor tyrosine kinase inhibitors in solid tumors: can we improve the cancer fighting strategy by blocking autophagy? Cancer Cell Int 16, 1–8 (2016).

doi: 10.1186/s12935-016-0341-2

Sun, X. et al. Receptor tyrosine kinase phosphorylation pattern–based multidrug combination is an effective approach for personalized cancer treatment. Mol. Cancer Ther. 15, 2508–2520 (2016).

pubmed: 27458140 doi: 10.1158/1535-7163.MCT-15-0735

Yao, Z. et al. A global analysis of the receptor tyrosine kinase-protein phosphatase interactome. Mol. Cell 65, 347–360 (2017).

pubmed: 28065597 pmcid: 5663465 doi: 10.1016/j.molcel.2016.12.004

Paul, M. D. & Hristova, K. The RTK interactome: overview and perspective on RTK heterointeractions. Chem. Rev. 119, 5881–5921 (2019).

pubmed: 30589534 doi: 10.1021/acs.chemrev.8b00467

Li, S. C. et al. High-affinity binding of the Drosophila Numb phosphotyrosine-binding domain to peptides containing a Gly-Pro-(p)Tyr motif. Proc. Natl Acad. Sci. USA 94, 7204–7209 (1997).

pubmed: 9207069 pmcid: 23792 doi: 10.1073/pnas.94.14.7204

Li, S. C. et al. Characterization of the phosphotyrosine-binding domain of the Drosophila Shc protein. J. Biol. Chem. 271, 31855–31862 (1996).

pubmed: 8943228 doi: 10.1074/jbc.271.50.31855

Xu, A. M. & Huang, P. H. Receptor tyrosine kinase coactivation networks in cancer. Cancer Res. 70, 3857–3860 (2010).

pubmed: 20406984 pmcid: 2875162 doi: 10.1158/0008-5472.CAN-10-0163

Fiorini, M., Alimandi, M., Fiorentino, L., Sala, G. & Segatto, O. Negative regulation of receptor tyrosine kinase signals. FEBS Lett. 490, 132–141 (2001).

pubmed: 11223028 doi: 10.1016/S0014-5793(01)02116-0

Phillips-Mason, P. J., Craig, S. E. L. & Brady-Kalnay, S. M. Should I stay or should I go? Shedding of RPTPs in cancer cells switches signals from stabilizing cell-cell adhesion to driving cell migration. Cell Adh Migr. 5, 298–305 (2011).

pubmed: 21785275 pmcid: 3210297 doi: 10.4161/cam.5.4.16970

Tang, R., Langdon, W. Y. & Zhang, J. Negative regulation of receptor tyrosine kinases by ubiquitination: key roles of the Cbl family of E3 ubiquitin ligases. Front. Endocrinol 13, (2022).

Casaletto, J. B. & McClatchey, A. I. Spatial regulation of receptor tyrosine kinases in development and cancer. Nat. Rev. Cancer 12, 387–400 (2012).

pubmed: 22622641 pmcid: 3767127 doi: 10.1038/nrc3277

Du, Z. & Lovly, C. M. Mechanisms of receptor tyrosine kinase activation in cancer. Mol. Cancer 17, 1–13 (2018).

doi: 10.1186/s12943-018-0782-4

Butti, R. et al. Receptor tyrosine kinases (RTKs) in breast cancer: signaling, therapeutic implications and challenges. Mol. Cancer 17, 34 (2018).

pubmed: 29455658 pmcid: 5817867 doi: 10.1186/s12943-018-0797-x

Ferrara, N., Gerber, H.-P. & LeCouter, J. The biology of VEGF and its receptors. Nat. Med. 9, 669–676 (2003).

pubmed: 12778165 doi: 10.1038/nm0603-669

Ullah, R., Yin, Q., Snell, A. H. & Wan, L. RAF-MEK-ERK pathway in cancer evolution and treatment. Semin. Cancer Biol. 85, 123–154 (2022).

pubmed: 33992782 doi: 10.1016/j.semcancer.2021.05.010

Truong, T. H. & Carroll, K. S. Redox regulation of protein kinases. Crit. Rev. Biochem. Mol. Biol. 48, 332–356 (2013).

pubmed: 23639002 pmcid: 4358782 doi: 10.3109/10409238.2013.790873

Belov, A. A. & Mohammadi, M. Grb2, a double-edged sword of receptor tyrosine kinase signaling. Sci. Signal 5, 1–7 (2012).

doi: 10.1126/scisignal.2003576

Talukdar, S., Emdad, L., Das, S. K. & Fisher, P. B. EGFR: an essential receptor tyrosine kinase-regulator of cancer stem cells. Adv. Cancer Res. 147, 161–188 (2020).

pubmed: 32593400 doi: 10.1016/bs.acr.2020.04.003

Wei, Q., Qian, Y., Yu, J. & Wong, C. C. Metabolic rewiring in the promotion of cancer metastasis: mechanisms and therapeutic implications. Oncogene 39, 6139–6156 (2020).

pubmed: 32839493 pmcid: 7515827 doi: 10.1038/s41388-020-01432-7

Locasale, J. W. Metabolic rewiring drives resistance to targeted cancer therapy. Mol. Syst. Biol 8 (2012).

Jin, N. et al. Identification of metabolic vulnerabilities of receptor tyrosine kinases-driven cancer. Nat Commun. 10 (2019).

Lin, C.-C. et al. Receptor tyrosine kinases regulate signal transduction through a liquid-liquid phase separated state. Mol. Cell 82, 1089–1106 (2022).

pubmed: 35231400 pmcid: 8937303 doi: 10.1016/j.molcel.2022.02.005

Huang, H. Proteolytic cleavage of receptor tyrosine kinases. Biomolecules 11 (2021).

Bache, K. G., Slagsvold, T. & Stenmark, H. Defective downregulation of receptor tyrosine kinases in cancer. EMBO J. 23, 2707–2712 (2004).

pubmed: 15229652 pmcid: 514952 doi: 10.1038/sj.emboj.7600292

Hubbard, S. R. & Miller, W. T. Receptor tyrosine kinases: mechanisms of activation and signaling. Curr. Opin. Cell Biol. 19, 117–123 (2007).

pubmed: 17306972 pmcid: 2536775 doi: 10.1016/j.ceb.2007.02.010

Montor WR, Salas Arose, Melo FHM. Receptor tyrosine kinases and downstream pathways as druggable targets for cancer treatment: the current arsenal of inhibitors. Mol Cancer 17 (2018).

McDonell, L. M., Kernohan, K. D., Boycott, K. M. & Sawyer, S. L. Receptor tyrosine kinase mutations in developmental syndromes and cancer: two sides of the same coin. Hum. Mol. Genet. 24, 60–66 (2015).

doi: 10.1093/hmg/ddv254

Robinson, D. R., Wu, Y. M. & Lin, S. F. The protein tyrosine kinase family of the human genome. Oncogene 19, 5548–5557 (2000).

pubmed: 11114734 doi: 10.1038/sj.onc.1203957

Saraon, P. et al. Receptor tyrosine kinases and cancer: oncogenic mechanisms and therapeutic approaches. Oncogene 40, 4079–4093 (2021).

pubmed: 34079087 doi: 10.1038/s41388-021-01841-2

Sheffels, E. & Kortum, R. L. Breaking oncogene addiction: getting RTK/RAS-mutated cancers off the SOS. J. Med. Chem. 64, 6566–6568 (2021).

pubmed: 33961431 doi: 10.1021/acs.jmedchem.1c00698

Orlando, E. et al. An oncogene addiction phosphorylation signature and its derived scores inform tumor responsiveness to targeted therapies. Cell Mol. Life Sci. 80 (2023).

Weinstein, I. B. Addiction to oncogenes-the Achilles heal of cancer. Science 297, 63–64 (2002).

pubmed: 12098689 doi: 10.1126/science.1073096

Vogelstein, B. et al. Cancer genome landscapes. Science 339, 1546–1558 (2013).

pubmed: 23539594 pmcid: 3749880 doi: 10.1126/science.1235122

Medves, S. & Demoulin, J. Tyrosine kinase gene fusions in cancer: translating mechanisms into targeted therapies. J. Cell Mol. Med. 16, 237–248 (2012).

pubmed: 21854543 pmcid: 3823288 doi: 10.1111/j.1582-4934.2011.01415.x

Ebrahimi, N. et al. Receptor tyrosine kinase inhibitors in cancer. Cell Mol. Life Sci. 80, (2023).

Lin, C.-C., Suen, K. M., Lidster, J. & Ladbury, J. E. The emerging role of receptor tyrosine kinase phase separation in cancer. Trends Cell Biol. 34, 371–379 (2023).

pubmed: 37777392 doi: 10.1016/j.tcb.2023.09.002

Jaradat, S. K., Ayoub, N. M., Al Sharie, A. H. & Aldaod, J. M. Targeting receptor tyrosine kinases as a novel strategy for the treatment of triple-negative breast cancer. Technol. Cancer Res. Treat. 23 (2024).

Labani-Motlagh, A., Ashja-Mahdavi, M. & Loskog, A. The tumor microenvironment: a milieu hindering and obstructing antitumor immune responses. Front. Immunol. 11 (2020).

Gaspar, N. et al. Lenvatinib with etoposide plus ifosfamide in patients with refractory or relapsed osteosarcoma (ITCC-050): a multicentre, open-label, multicohort, phase 1/2 study. Lancet Oncol. 22, 1312–1321 (2021).

pubmed: 34416158 doi: 10.1016/S1470-2045(21)00387-9

Zhang, N. & Li, Y. Receptor tyrosine kinases: biological functions and anticancer targeted therapy. MedComm 4 (2023).

Wirth, T. A role for RTKs in Hodgkin lymphoma. Blood 105, 3766–3766 (2005).

doi: 10.1182/blood-2005-02-0826

Gupta, R., Knight, C. L. & Bain, B. J. Receptor tyrosine kinase mutations in myeloid neoplasms. Br. J. Haematol. 117, 489–508 (2002).

pubmed: 12028015 doi: 10.1046/j.1365-2141.2002.03469.x

Kim, Y. et al. Temporal resolution of autophosphorylation for normal and oncogenic forms of EGFR and differential effects of gefitinib. Biochemistry 51, 5212–5222 (2012).

pubmed: 22657099 doi: 10.1021/bi300476v

Ferguson, K. M., Hu, C. & Lemmon, M. A. Insulin and epidermal growth factor receptor family members share parallel activation mechanisms. Protein Sci. 29, 1331–1344 (2020).

pubmed: 32297376 pmcid: 7255510 doi: 10.1002/pro.3871

Cohen, S. The epidermal growth factor (EGF). Cancer 51, 1787–1791 (1983).

pubmed: 6299497 doi: 10.1002/1097-0142(19830515)51:10<1787::AID-CNCR2820511004>3.0.CO;2-A

Roskoski, R. ErbB/HER protein-tyrosine kinases: Structures and small molecule inhibitors. Pharm. Res. 87, 42–59 (2014).

doi: 10.1016/j.phrs.2014.06.001

Ceresa, B. P. & Peterson, J. L. Cell and molecular biology of epidermal growth factor receptor. Int. Rev. Cell Mol. Biol. 313, 145–178 (2014).

pubmed: 25376492 doi: 10.1016/B978-0-12-800177-6.00005-0

Ullrich, A. et al. Human epidermal growth factor receptor cDNA sequence and aberrant expression of the amplified gene in A431 epidermoid carcinoma cells. Nature 309, 418–425 (1984).

pubmed: 6328312 doi: 10.1038/309418a0

Yarden, Y. & Pines, G. The ERBB network: at last, cancer therapy meets systems biology. Nat. Rev. Cancer 12, 553–563 (2012).

pubmed: 22785351 doi: 10.1038/nrc3309

Jorissen, R. N. et al. Epidermal growth factor receptor: mechanisms of activation and signalling. Exp. Cell Res. 284, 31–53 (2003).

pubmed: 12648464 doi: 10.1016/S0014-4827(02)00098-8

Rosenkranz, A. A. & Slastnikova, T. A. Epidermal growth factor receptor: key to selective intracellular delivery. Biochemistry (Mosc) 85, 967–1092 (2020).

pubmed: 33050847 doi: 10.1134/S0006297920090011

Arteaga, C. L. & Engelman, J. A. ERBB receptors: from oncogene discovery to basic science to mechanism-based cancer therapeutics. Cancer Cell 25, 282–303 (2014).

pubmed: 24651011 pmcid: 4018830 doi: 10.1016/j.ccr.2014.02.025

Arienti, C., Pignatta, S. & Tesei, A. Epidermal growth factor receptor family and its role in gastric cancer. Front. Oncol. 9 (2019).

Thompson, D. M. & Gill, G. N. The EGF receptor: structure, regulation and potential role in malignancy. Cancer Surv. 4, 767–788 (1985).

pubmed: 2824044

Reschke, M. et al. HER3 is a determinant for poor prognosis in melanoma. Clin. Cancer Res. 14, 5188–5197 (2008).

pubmed: 18698037 doi: 10.1158/1078-0432.CCR-08-0186

Koumakpayi, I. H. et al. Expression and nuclear localization of ErbB3 in prostate cancer. Clin. Cancer Res. 12, 2730–2737 (2006).

pubmed: 16675564 doi: 10.1158/1078-0432.CCR-05-2242

Tanner, B. et al. ErbB-3 predicts survival in ovarian cancer. J. Clin. Oncol. 24, 4317–4323 (2006).

pubmed: 16896008 doi: 10.1200/JCO.2005.04.8397

Wei, Q. et al. EGFR, HER2 and HER3 expression in esophageal primary tumours and corresponding metastases. Int. J. Oncol. 31, 493–499 (2007).

pubmed: 17671674

Wei, Q. et al. EGFR, HER2, and HER3 expression in laryngeal primary tumors and corresponding metastases. Ann. Surg. Oncol. 15, 1193–1201 (2008).

pubmed: 18172732 doi: 10.1245/s10434-007-9771-3

Kapitanović, S. et al. Expression of erbB-3 protein in colorectal adenocarcinoma: correlation with poor survival. J. Cancer Res. Clin. Oncol. 126, 205–211 (2000).

pubmed: 10782893 doi: 10.1007/s004320050034

Witton, C. J., Reeves, J. R., Going, J. J., Cooke, T. G. & Bartlett, J. M. S. Expression of the HER1-4 family of receptor tyrosine kinases in breast cancer. J. Pathol. 200, 290–297 (2003).

pubmed: 12845624 doi: 10.1002/path.1370

Cancer Genome Atlas Network. Comprehensive molecular characterization of human colon and rectal cancer. Nature 487, 330–337 (2012).

doi: 10.1038/nature11252

Russo, A. et al. A decade of EGFR inhibition in EGFR-mutated non small cell lung cancer (NSCLC): old successes and future perspectives. Oncotarget 6, 26814–26825 (2015).

pubmed: 26308162 pmcid: 4694955 doi: 10.18632/oncotarget.4254

Nahm, C. B. et al. Biomarker panel predicts survival after resection in pancreatic ductal adenocarcinoma: a multi-institutional cohort study. Eur. J. Surg. Oncol. 45, 218–224 (2019).

pubmed: 30348604 doi: 10.1016/j.ejso.2018.10.050

Ueda, S. et al. The correlation between cytoplasmic overexpression of epidermal growth factor receptor and tumor aggressiveness: poor prognosis in patients with pancreatic ductal adenocarcinoma. Pancreas 29, 1–8 (2004).

doi: 10.1097/00006676-200407000-00061

Wang, Z. ErbB receptors and cancer. Methods Mol. Biol. 1652, 3–35 (2017).

pubmed: 28791631 doi: 10.1007/978-1-4939-7219-7_1

Shah, R. B., Ghosh, D. & Elder, J. T. Epidermal growth factor receptor (ErbB1) expression in prostate cancer progression: correlation with androgen independence. Prostate 66, 1437–1444 (2006).

pubmed: 16741920 doi: 10.1002/pros.20460

Yu, H. A. et al. Analysis of tumor specimens at the time of acquired resistance to EGFR-TKI therapy in 155 patients with EGFR -mutant lung cancers. Clin. Cancer Res. 19, 2240–2247 (2013).

pubmed: 23470965 pmcid: 3630270 doi: 10.1158/1078-0432.CCR-12-2246

Yamaura, T. et al. Genetic alterations in epidermal growth factor receptor-tyrosine kinase inhibitor-naïve non-small cell lung carcinoma. Oncol. Lett. 19, 4169–4176 (2020).

pubmed: 32391110 pmcid: 7204631

Zheng, D. et al. EGFR G796D mutation mediates resistance to osimertinib. Oncotarget 8, 49671–49679 (2017).

pubmed: 28572531 pmcid: 5564797 doi: 10.18632/oncotarget.17913

Fu, K., Xie, F., Wang, F. & Fu, L. Therapeutic strategies for EGFR-mutated non-small cell lung cancer patients with osimertinib resistance. J. Hematol. Oncol. 15 (2022).

Liu, H., Zhang, B. & Sun, Z. Spectrum of EGFR aberrations and potential clinical implications: insights from integrative pan-cancer analysis. Cancer Commun. 40, 43–59 (2020).

doi: 10.1002/cac2.12005

Wang, F. et al. Identification of genetic alterations associated with primary resistance to EGFR-TKIs in advanced non-small-cell lung cancer patients with EGFR sensitive mutations. Cancer Commun. 39, 1–15 (2019).

Chakravarty, D. et al. OncoKB: a precision oncology knowledge base. JCO Precis. Oncol. 2017 (2017).

Jebali, A. & Dumaz, N. The role of RICTOR downstream of receptor tyrosine kinase in cancers. Mol. Cancer 17 (2018).

Mikhaylenko, D. S., Alekseev, B. Y., Zaletaev, D. V., Goncharova, R. I. & Nemtsova, M. V. Structural alterations in human fibroblast growth factor receptors in carcinogenesis. Biochemistry 83, 930–943 (2018).

pubmed: 30208830

Babina, I. S. & Turner, N. C. Advances and challenges in targeting FGFR signalling in cancer. Nat. Rev. Cancer 17, 318–332 (2017).

pubmed: 28303906 doi: 10.1038/nrc.2017.8

Helsten, T. et al. The FGFR landscape in cancer: analysis of 4,853 tumors by next-generation sequencing. Clin. Cancer Res. 22, 259–267 (2016).

pubmed: 26373574 doi: 10.1158/1078-0432.CCR-14-3212

Ferguson, H. R., Smith, M. P. & Francavilla, C. Fibroblast growth factor receptors (FGFRs) and noncanonical partners in cancer signaling. Cells 10, 1–35 (2021).

doi: 10.3390/cells10051201

Krook, M. A. et al. Fibroblast growth factor receptors in cancer: genetic alterations, diagnostics, therapeutic targets and mechanisms of resistance. Br. J. Cancer 124, 880–892 (2021).

pubmed: 33268819 doi: 10.1038/s41416-020-01157-0

Sobhani, N. et al. Current status of fibroblast growth factor receptor-targeted therapies in breast cancer. Cells 7 (2018).

Imamura, T. Physiological functions and underlying mechanisms of fibroblast growth factor (FGF) family members: recent findings and implications for their pharmacological application. Biol. Pharm. Bull. 37, 1081–1089 (2014).

pubmed: 24988999 doi: 10.1248/bpb.b14-00265

Qin, A. et al. Detection of known and novel FGFR fusions in non-small cell lung cancer by comprehensive genomic profiling. J. Thorac. Oncol. 14, 54–62 (2019).

pubmed: 30267839 doi: 10.1016/j.jtho.2018.09.014

André, F. & Cortés, J. Rationale for targeting fibroblast growth factor receptor signaling in breast cancer. Breast Cancer Res. Treat. 150, 1–8 (2015).

pubmed: 25677745 pmcid: 4344551 doi: 10.1007/s10549-015-3301-y

Gallo, L. H., Nelson, K. N., Meyer, A. N. & Donoghue, D. J. Functions of fibroblast growth factor receptors in cancer defined by novel translocations and mutations. Cytokine Growth Factor Rev. 26, 425–449 (2015).

pubmed: 26003532 doi: 10.1016/j.cytogfr.2015.03.003

Rosty, C. et al. Clinical and biological characteristics of cervical neoplasias with FGFR3 mutation. Mol. Cancer 4 (2005).

Hernández, S. et al. Prospective study of FGFR3 mutations as a prognostic factor in nonmuscle invasive urothelial bladder carcinomas. J. Clin. Oncol. 24, 3664–3671 (2006).

pubmed: 16877735 doi: 10.1200/JCO.2005.05.1771

Ruhe, J. E. et al. Genetic alterations in the tyrosine kinase transcriptome of human cancer cell lines. Cancer Res. 67, 11368–11376 (2007).

pubmed: 18056464 doi: 10.1158/0008-5472.CAN-07-2703

Tang, S., Hao, Y., Yuan, Y., Liu, R. & Chen, Q. Role of fibroblast growth factor receptor 4 in cancer. Cancer Sci. 109, 3024–3031 (2018).

pubmed: 30070748 pmcid: 6172014 doi: 10.1111/cas.13759

Patani, H. et al. Landscape of activating cancer mutations in FGFR kinases and their differential responses to inhibitors in clinical use. Oncotarget 7, 24252–24268 (2016).

pubmed: 26992226 pmcid: 5029699 doi: 10.18632/oncotarget.8132

Katoh, M. Fibroblast growth factor receptors as treatment targets in clinical oncology. Nat. Rev. Clin. Oncol. 16, 105–122 (2019).

pubmed: 30367139 doi: 10.1038/s41571-018-0115-y

Stransky, N. et al. The mutational landscape of head and neck squamous cell carcinoma. Science 333, 1157–1160 (2011).

pubmed: 21798893 pmcid: 3415217 doi: 10.1126/science.1208130

Greenman, C. et al. Patterns of somatic mutation in human cancer genomes. Nature 446, 153–158 (2007).

pubmed: 17344846 pmcid: 2712719 doi: 10.1038/nature05610

The Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature 490, 61–70 (2012).

Belfiore, A. The role of insulin receptor isoforms and hybrid insulin/IGF-I receptors in human cancer. Curr. Pharm. Des. 13, 671–686 (2007).

pubmed: 17346183 doi: 10.2174/138161207780249173

Pisani, P. Hyper-insulinaemia and cancer, meta-analyses of epidemiological studies. Arch. Physiol. Biochem 114, 63–70 (2008).

pubmed: 18465360 doi: 10.1080/13813450801954451

Kim, D.-S. & Scherer, P. E. Obesity, diabetes, and increased cancer progression. Diabetes Metab. J. 45, 799–812 (2021).

pubmed: 34847640 pmcid: 8640143 doi: 10.4093/dmj.2021.0077

Scully, T., Ettela, A., LeRoith, D. & Gallagher, E. J. Obesity, type 2 diabetes, and cancer risk. Front. Oncol. 10 (2020).

Hers, I., Vincent, E. E. & Tavaré, J. M. Akt signalling in health and disease. Cell Signal 23, 1515–1527 (2011).

pubmed: 21620960 doi: 10.1016/j.cellsig.2011.05.004

Drakas, R., Tu, X. & Baserga, R. Control of cell size through phosphorylation of upstream binding factor 1 by nuclear phosphatidylinositol 3-kinase. Proc. Natl Acad. Sci. USA 101, 9272–9276 (2004).

pubmed: 15197263 pmcid: 438966 doi: 10.1073/pnas.0403328101

Ullrich, A. et al. Human insulin receptor and its relationship to the tyrosine kinase family of oncogenes. Nature 313, 756–761 (1985).

pubmed: 2983222 doi: 10.1038/313756a0

Ebina, Y. et al. Expression of a functional human insulin receptor from a cloned cDNA in Chinese hamster ovary cells. Proc. Natl Acad. Sci. USA 82, 8014–8018 (1985).

pubmed: 3906655 pmcid: 391432 doi: 10.1073/pnas.82.23.8014

Malaguarnera, R. & Belfiore, A. The insulin receptor: a new target for cancer therapy. Front. Endocrinol. 2 (2011).

Ullrich, A. et al. Insulin-like growth factor I receptor primary structure: comparison with insulin receptor suggests structural determinants that define functional specificity. EMBO J. 5, 2503–2512 (1986).

pubmed: 2877871 pmcid: 1167146 doi: 10.1002/j.1460-2075.1986.tb04528.x

Nakae, J., Kido, Y. & Accili, D. Distinct and overlapping functions of insulin and IGF-I receptors. Endocr. Rev. 22, 818–835 (2001).

pubmed: 11739335 doi: 10.1210/edrv.22.6.0452

Reeves, R., Edberg, D. D. & Li, Y. Architectural transcription factor HMGI(Y) promotes tumor progression and mesenchymal transition of human epithelial cells. Mol. Cell Biol. 21, 575–594 (2001).

pubmed: 11134344 pmcid: 86623 doi: 10.1128/MCB.21.2.575-594.2001

Aiello, A. et al. HMGA1 protein is a positive regulator of the insulin-like growth factor-I receptor gene. Eur. J. Cancer 46, 1919–1926 (2010).

pubmed: 20335021 doi: 10.1016/j.ejca.2010.02.050

Paul, S. et al. Interaction of muscleblind, CUG-BP1 and hnRNP H proteins in DM1-associated aberrant IR splicing. EMBO J. 25, 4271–4283 (2006).

pubmed: 16946708 pmcid: 1570429 doi: 10.1038/sj.emboj.7601296

Craddock, B. P. & Miller, W. T. Effects of somatic mutations in the C-terminus of insulin-like growth factor 1 receptor on activity and signaling. J. Signal. Transduct 2012, 1–7 (2012).

doi: 10.1155/2012/804801

Gorgisen, G. et al. Identification of novel mutations of Insulin Receptor Substrate 1 (IRS1) in tumor samples of non-small cell lung cancer (NSCLC): Implications for aberrant insulin signaling in development of cancer. Genet Mol. Biol. 42, 15–25 (2019).

pubmed: 30807634 pmcid: 6428125 doi: 10.1590/1678-4685-gmb-2017-0307

Hamilton, T. G., Klinghoffer, R. A., Corrin, P. D. & Soriano, P. Evolutionary divergence of platelet-derived growth factor alpha receptor signaling mechanisms. Mol. Cell Biol. 23, 4013–4025 (2003).

pubmed: 12748302 pmcid: 155222 doi: 10.1128/MCB.23.11.4013-4025.2003

Dell, S., Peters, S., Müther, P., Kociok, N. & Joussen, A. M. The role of PDGF receptor inhibitors and PI3-kinase signaling in the pathogenesis of corneal neovascularization. Investig. Ophthalmol. Vis. Sci. 47, 1928–1937 (2006).

doi: 10.1167/iovs.05-1071

Lokker, N. A. et al. Functional importance of platelet-derived growth factor (PDGF) receptor extracellular immunoglobulin-like domains. Identification of PDGF binding site and neutralizing monoclonal antibodies. J. Biol. Chem. 272, 33037–33044 (1997).

pubmed: 9407086 doi: 10.1074/jbc.272.52.33037

Manzat Saplacan, R. M. et al. The role of PDGFs and PDGFRs in colorectal cancer. Mediators Inflamm. 2017, (2017).

Sheikh, E., Tran, T., Vranic, S., Levy, A. & Bonfil, R. D. Role and significance of c-KIT receptor tyrosine kinase in cancer: A review. Bosn. J. Basic Med Sci. 22, 683–698 (2022).

pubmed: 35490363 pmcid: 9519160

Heldin, C.-H. & Lennartsson, J. Receptor tyrosine kinases and their ligands. in Encyclopedia of Cell Biology Vol. 3, 8–21 (Elsevier, 2016).

Hirota, S. et al. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science 279, 577–580 (1998).

pubmed: 9438854 doi: 10.1126/science.279.5350.577

Bahlawane, C. et al. Constitutive activation of oncogenic PDGFRα-mutant proteins occurring in GIST patients induces receptor mislocalisation and alters PDGFRα signalling characteristics. Cell Commun. Signal. 13 (2015).

Ravegnini, G. et al. miRNA expression may have implications for immunotherapy in PDGFRA mutant GISTs. Int. J. Mol. Sci. 23 (2022).

Prenen, H. et al. Efficacy of the kinase inhibitor SU11248 against gastrointestinal stromal tumor mutants refractory to imatinib mesylate. Clin. Cancer Res. 12, 2622–2627 (2006).

pubmed: 16638875 doi: 10.1158/1078-0432.CCR-05-2275

Ip, C. K. M. et al. Neomorphic PDGFRA extracellular domain driver mutations are resistant to PDGFRA-targeted therapies. Nat. Commun. 9, 1–14 (2018).

doi: 10.1038/s41467-018-06949-w

Heinrich, M. C. et al. Crenolanib inhibits the drug-resistant PDGFRA D842V mutation associated with imatinib-resistant gastrointestinal stromal tumors. Clin. Cancer Res. 18, 4375–4384 (2012).

pubmed: 22745105 doi: 10.1158/1078-0432.CCR-12-0625

Weisberg, E. et al. Effects of PKC412, Nilotinib, and Imatinib Against GIST-Associated PDGFRA Mutants With Differential Imatinib Sensitivity. Gastroenterology 131, 1734–1742 (2006).

pubmed: 17087936 doi: 10.1053/j.gastro.2006.09.017

Burger, K. et al. Activating mutations in c-KIT and PDGFRα are exclusively found in gastrointestinal stromal tumors and not in other tumors overexpressing these imatinib mesylate target genes. Cancer Biol. Ther. 4, 1270–1274 (2005).

pubmed: 16294026 doi: 10.4161/cbt.4.11.2253

Guérit, E., Arts, F., Dachy, G., Boulouadnine, B. & Demoulin, J.-B. PDGF receptor mutations in human diseases. Cell Mol. Life Sci. 78, 3867–3881 (2021).

pubmed: 33449152 pmcid: 11072557 doi: 10.1007/s00018-020-03753-y

Paugh, B. S. et al. Novel oncogenic PDGFRA mutations in pediatric high-grade gliomas. Cancer Res. 73, 6219–6229 (2013).

pubmed: 23970477 pmcid: 3800209 doi: 10.1158/0008-5472.CAN-13-1491

Reindl, C. et al. Point mutations in the juxtamembrane domain of FLT3 define a new class of activating mutations in AML. Blood 107, 3700–3707 (2006).

pubmed: 16410449 doi: 10.1182/blood-2005-06-2596

Rizzo, A., Pantaleo, M. A., Astolfi, A., Indio, V. & Nannini, M. The identity of PDGFRA D842V-mutant gastrointestinal stromal tumors (GIST). Cancers 13 (2021).

Alitalo, K. & Carmeliet, P. Molecular mechanisms of lymphangiogenesis in health and disease. Cancer Cell 1, 219–227 (2002).

pubmed: 12086857 doi: 10.1016/S1535-6108(02)00051-X

Shibuya, M. Vascular endothelial growth factor (VEGF) and its receptor (VEGFR) signaling in angiogenesis: a crucial target for anti- and pro-angiogenic therapies. Genes Cancer 2, 1097–1105 (2011).

pubmed: 22866201 pmcid: 3411125 doi: 10.1177/1947601911423031

Zhu, X., Zhou, W. The emerging regulation of VEGFR-2 in triple-negative breast cancer. Front Endocrinol. 6 (2015).

Mokhdomi, T. A. et al. A novel kinase mutation in VEGFR-1 predisposes its αC-helix/activation loop towards allosteric activation: Atomic insights from protein simulation. Eur. J. Hum. Genet. 24, 1287–1293 (2016).

pubmed: 27049304 pmcid: 4989210 doi: 10.1038/ejhg.2016.26

Scartozzi, M. et al. Role of vascular endothelial growth factor (VEGF) and VEGF-R genotyping in guiding the metastatic process in pT4a resected gastric cancer patients. PLoS One 7, 1–7 (2012).

doi: 10.1371/journal.pone.0038192

Grillo, E. et al. A novel variant of VEGFR2 identified by a pan-cancer screening of recurrent somatic mutations in the catalytic domain of tyrosine kinase receptors enhances tumor growth and metastasis. Cancer Lett. 496, 84–92 (2021).

pubmed: 33035615 doi: 10.1016/j.canlet.2020.09.027

Grillo, E. et al. Expression of activated VEGFR2 by R1051Q mutation alters the energy metabolism of Sk-Mel-31 melanoma cells by increasing glutamine dependence. Cancer Lett. 507, 80–88 (2021).

pubmed: 33744390 doi: 10.1016/j.canlet.2021.03.007

Sarabipour, S., Ballmer-Hofer, K. & Hristova, K. VEGFR-2 conformational switch in response to ligand binding. Elife 5 (2016).

Boye, E., Jinnin, M. & Olsen, B. R. Infantile hemangioma. J. Craniofac. Surg. 20, 678–684 (2009).

pubmed: 19190505 doi: 10.1097/SCS.0b013e318193d6c1

Zhu, X. et al. The VEGFR-2 protein and the VEGFR-2 rs1870377 A>T genetic polymorphism are prognostic factors for gastric cancer. Cancer Biol. Ther. 20, 497–504 (2019).

pubmed: 30380970 doi: 10.1080/15384047.2018.1537575

Maeng, C. H. et al. Effects of single nucleotide polymorphisms on treatment outcomes and toxicity in patients treated with sunitinib. Anticancer Res. 33, 4619–4626 (2013).

pubmed: 24123039

Hansen, T. F. et al. Microvessel density and the association with single nucleotide polymorphisms of the vascular endothelial growth factor receptor 2 in patients with colorectal cancer. Virchows Arch. 456, 251–260 (2010).

pubmed: 20143086 doi: 10.1007/s00428-009-0878-8

Cho, S.-J., Park, M. H., Han, C., Yoon, K. & Koh, Y. H. VEGFR2 alteration in Alzheimer’s disease. Sci. Rep. 7 (2017).

Hsu, M.-C., Pan, M.-R. & Hung, W.-C. Two birds, one stone: double hits on tumor growth and lymphangiogenesis by targeting vascular endothelial growth factor receptor 3. Cells 8 (2019).

Karkkainen, M. J. et al. Missense mutations interfere with VEGFR-3 signalling in primary lymphoedema. Nat. Genet. 25, 153–159 (2000).

pubmed: 10835628 doi: 10.1038/75997

Gordon, K. et al. FLT4/VEGFR3 and Milroy disease: novel mutations, a review of published variants and database update. Hum. Mutat. 34, 23–31 (2013).

pubmed: 23074044 doi: 10.1002/humu.22223

Gu, Y. et al. Case report: Unique FLT4 variants associated with differential response to anlotinib in angiosarcoma. Front. Oncol. 12 (2022).

Feng, Y., Yang, Z. & Xu, X. c-Met: a promising therapeutic target in bladder cancer. Cancer Manag. Res. 14, 2379–2388 (2022).

pubmed: 35967753 pmcid: 9374328 doi: 10.2147/CMAR.S369175

Wang, M.-H., Zhou, Y.-Q. & Chen, Y.-Q. Macrophage-stimulating protein and RON receptor tyrosine kinase: potential regulators of macrophage inflammatory activities. Scand. J. Immunol. 56, 545–553 (2002).

pubmed: 12472665 doi: 10.1046/j.1365-3083.2002.01177.x

Wang, M.-H., Lee, W., Luo, Y.-L., Weis, M. T. & Yao, H.-P. Altered expression of the RON receptor tyrosine kinase in various epithelial cancers and its contribution to tumourigenic phenotypes in thyroid cancer cells. J. Pathol. 213, 402–411 (2007).

pubmed: 17955509 doi: 10.1002/path.2245

Zhou, Y.-Q., He, C., Chen, Y.-Q., Wang, D. & Wang, M.-H. Altered expression of the RON receptor tyrosine kinase in primary human colorectal adenocarcinomas: generation of different splicing RON variants and their oncogenic potential. Oncogene 22, 186–197 (2003).

pubmed: 12527888 doi: 10.1038/sj.onc.1206075

Cheng, H.-L. et al. Co-expression of RON and MET is a prognostic indicator for patients with transitional-cell carcinoma of the bladder. Br. J. Cancer 92, 1906–1914 (2005).

pubmed: 15870710 pmcid: 2361770 doi: 10.1038/sj.bjc.6602593

Maggiora, P. et al. The RON and MET oncogenes are co-expressed in human ovarian carcinomas and cooperate in activating invasiveness. Exp. Cell Res. 288, 382–389 (2003).

pubmed: 12915129 doi: 10.1016/S0014-4827(03)00250-7

Johnson, M. et al. Selective tumorigenesis in non-parenchymal liver epithelial cell lines by hepatocyte growth factor transfection. Cancer Lett. 96, 37–48 (1995).

pubmed: 7553606 doi: 10.1016/0304-3835(95)03915-J

Sattler, M., Reddy, M. M., Hasina, R., Gangadhar, T. & Salgia, R. The role of the c-Met pathway in lung cancer and the potential for targeted therapy. Ther. Adv. Med. Oncol. 3, 171–184 (2011).

pubmed: 21904579 pmcid: 3150066 doi: 10.1177/1758834011408636

Weidner, K. M. et al. Interaction between Gab1 and the c-Met receptor tyrosine kinase is responsible for epithelial morphogenesis. Nature 384, 173–176 (1996).

pubmed: 8906793 doi: 10.1038/384173a0

Jeffers, M. et al. Hepatocyte growth factor/scatter factor-Met signaling induces proliferation, migration, and morphogenesis of pancreatic oval cells. Cell Growth Differ. 7, 1805–1813 (1996).

pubmed: 8959349

Rong, S., Segal, S., Anver, M., Resau, J. H. & Vande Woude, G. F. Invasiveness and metastasis of NIH 3T3 cells induced by Met-hepatocyte growth factor/scatter factor autocrine stimulation. Proc. Natl Acad. Sci. USA 91, 4731–4735 (1994).

pubmed: 8197126 pmcid: 43862 doi: 10.1073/pnas.91.11.4731

Zarnegar, R. Regulation of HGF and HGFR gene expression. Epithelial-Mesenchymal Interactions in Cancer (eds. Goldberg, I. D., & Rosen, E. M.) vol. 74 33–49 (Experientia Supplementum, 1995).

Shieh, J.-M. et al. Lack of association of C-Met-N375S sequence variant with lung cancer susceptibility and prognosis. Int. J. Med. Sci. 10, 988–994 (2013).

pubmed: 23801885 pmcid: 3691797 doi: 10.7150/ijms.5944

Kong, L. R., Binte Mohamed Salleh, N. A., Tan, T. Z., Kappei, D. & Goh, B. C. P1.02-041 characterization of MET-N375S as an activating mutation in squamous cell carcinoma of the lung. J. Thorac. Oncol. 12, S512–S512 (2017).

doi: 10.1016/j.jtho.2016.11.624

Jagadeeswaran, R. et al. Functional analysis of c-Met/hepatocyte growth factor pathway in malignant pleural mesothelioma. Cancer Res. 66, 352–361 (2006).

pubmed: 16397249 doi: 10.1158/0008-5472.CAN-04-4567

Xu, T.-X. et al. cMET-N375S germline mutation is associated with poor prognosis of melanoma in Chinese patients. Transl. Cancer Res. 7, 248–256 (2018).

doi: 10.21037/tcr.2018.02.13

Cortot, A. B. et al. Exon 14 deleted MET receptor as a new biomarker and target in cancers. J. Natl Cancer Inst. 109 (2017).

Tyner, J. W. et al. MET receptor sequence variants R970C and T992I lack transforming capacity. Cancer Res. 70, 6233–6237 (2010).

pubmed: 20670955 pmcid: 2913476 doi: 10.1158/0008-5472.CAN-10-0429

Neklason, D. W. et al. Activating mutation in MET oncogene in familial colorectal cancer. BMC Cancer 11 (2011).

Sadiq, A. A. & Salgia, R. MET as a possible target for non–small-cell lung cancer. J. Clin. Oncol. 31, 1089–1096 (2013).

pubmed: 23401458 pmcid: 3589702 doi: 10.1200/JCO.2012.43.9422

Blumenschein, G. R., Mills, G. B. & Gonzalez-Angulo, A. M. Targeting the hepatocyte growth factor–cMET axis in cancer therapy. J. Clin. Oncol. 30, 3287–3296 (2012).

pubmed: 22869872 pmcid: 3434988 doi: 10.1200/JCO.2011.40.3774

Jeffers, M. et al. Activating mutations for the Met tyrosine kinase receptor in human cancer. Proc. Natl Acad. Sci. USA 94, 11445–11450 (1997).

pubmed: 9326629 pmcid: 23495 doi: 10.1073/pnas.94.21.11445

Iyer, A. et al. Structure, tissue-specific expression, and transforming activity of the mouse met protooncogene. Cell Growth Differ. 1, 87–95 (1990).

pubmed: 2085463

Di Renzo, M. F. et al. Expression of the Met/HGF receptor in normal and neoplastic human tissues. Oncogene 6, 1997–2003 (1991).

pubmed: 1719465

Kan, M. et al. Hepatocyte growth factor/hepatopoietin A stimulates the growth of rat kidney proximal tubule epithelial cells (RPTE), rat nonparenchymal liver cells, human melanoma cells, mouse keratinocytes and stimulates anchorage-independent growth of SV-40 transformed RPTE. Biochem. Biophys. Res. Commun. 174, 331–337 (1991).

pubmed: 1846541 doi: 10.1016/0006-291X(91)90524-B

Schmidt, L. et al. Germline and somatic mutations in the tyrosine kinase domain of the MET proto-oncogene in papillary renal carcinomas. Nat. Genet. 16, 68–73 (1997).

pubmed: 9140397 doi: 10.1038/ng0597-68

Zeng, Z.-S. et al. c-Met gene amplification is associated with advanced stage colorectal cancer and liver metastases. Cancer Lett. 265, 258–269 (2008).

pubmed: 18395971 pmcid: 4367187 doi: 10.1016/j.canlet.2008.02.049

Nakamura, M. et al. Hepatocyte growth factor secreted by ovarian cancer cells stimulates peritoneal implantation via the mesothelial–mesenchymal transition of the peritoneum. Gynecol. Oncol. 139, 345–354 (2015).

pubmed: 26335595 doi: 10.1016/j.ygyno.2015.08.010

Seidel, C. et al. Elevated serum concentrations of hepatocyte growth factor in patients with multiple myeloma. The Nordic Myeloma Study Group. Blood 91, 806–812 (1998).

pubmed: 9446640 doi: 10.1182/blood.V91.3.806

Sheen-Chen, S.-M., Liu, Y.-W., Eng, H.-L. & Chou, F.-F. Serum levels of hepatocyte growth factor in patients with breast cancer. Cancer Epidemiol. Biomark. Prev. 14, 715–717 (2005).

doi: 10.1158/1055-9965.EPI-04-0340

Xie, Q. et al. Hepatocyte growth factor (HGF) autocrine activation predicts sensitivity to MET inhibition in glioblastoma. Proc. Natl Acad. Sci. USA 109, 570–575 (2012).

pubmed: 22203985 doi: 10.1073/pnas.1119059109

Cruickshanks, N. et al. Role and therapeutic targeting of the HGF/MET pathway in glioblastoma. Cancers 9 (2017).

Borges, L. S. & Richman, D. P. Muscle-specific kinase myasthenia gravis. Front. Immunol. 11, 1–11 (2020).

doi: 10.3389/fimmu.2020.00707

Valenzuela, D. M. et al. Receptor tyrosine kinase specific for the skeletal muscle lineage: expression in embryonic muscle, at the neuromuscular junction, and after injury. Neuron 15, 573–584 (1995).

pubmed: 7546737 doi: 10.1016/0896-6273(95)90146-9

DeChiara, T. M. et al. The receptor tyrosine kinase MuSK is required for neuromuscular junction formation in vivo. Cell 85, 501–512 (1996).

pubmed: 8653786 doi: 10.1016/S0092-8674(00)81251-9

Gautam, M. et al. Defective neuromuscular synaptogenesis in agrin-deficient mutant mice. Cell 85, 525–535 (1996).

pubmed: 8653788 doi: 10.1016/S0092-8674(00)81253-2

Till, J. H. et al. Crystal structure of the MuSK tyrosine kinase: insights into receptor autoregulation. Structure 10, 1187–1196 (2002).

pubmed: 12220490 doi: 10.1016/S0969-2126(02)00814-6

Xie, T. et al. Structural insights into the assembly of the agrin/LRP4/MuSK signaling complex. Proc. Natl Acad. Sci. USA 120, 1–8 (2023).

doi: 10.1073/pnas.2300453120

Yang, J. et al. Nestin negatively regulates postsynaptic differentiation of the neuromuscular synapse. Nat. Neurosci. 14, 324–330 (2011).

pubmed: 21278733 pmcid: 3069133 doi: 10.1038/nn.2747

Koneczny, I., Cossins, J. & Vincent, A. The role of muscle-specific tyrosine kinase (MuSK) and mystery of MuSK myasthenia gravis. J. Anat. 224, 29–35 (2014).

pubmed: 23458718 doi: 10.1111/joa.12034

Hoch, W. et al. Auto-antibodies to the receptor tyrosine kinase MuSK in patients with myasthenia gravis without acetylcholine receptor antibodies. Nat. Med. 7, 365–368 (2001).

pubmed: 11231638 doi: 10.1038/85520

Ben Ammar, A. et al. A mutation causes MuSK reduced sensitivity to agrin and congenital myasthenia. PLoS One 8, (2013).

Spengos, K. et al. Dropped head syndrome as prominent clinical feature in MuSK-positive Myasthenia Gravis with thymus hyperplasia. Neuromuscul. Disord. 18, 175–177 (2008).

pubmed: 18053719 doi: 10.1016/j.nmd.2007.09.007

Golding, B., Luu, A., Jones, R. & Viloria-Petit, A. M. The function and therapeutic targeting of anaplastic lymphoma kinase (ALK) in non-small cell lung cancer (NSCLC). Mol Cancer 17 (2018).

Reshetnyak, A. V. et al. Mechanism for the activation of the anaplastic lymphoma kinase receptor. Nature 600, 153–157 (2021).

pubmed: 34819673 pmcid: 8639797 doi: 10.1038/s41586-021-04140-8

Omar, N. E. et al. Postmarketing safety of anaplastic lymphoma kinase (ALK) inhibitors: an analysis of the FDA Adverse Event Reporting System (FAERS). ESMO Open 6, 1–7 (2021).

doi: 10.1016/j.esmoop.2021.100315

Christova, T., Ho, S. K., Liu, Y., Gill, M. & Attisano, L. LTK and ALK promote neuronal polarity and cortical migration by inhibiting IGF1R activity. EMBO Rep. 24, 1–21 (2023).

doi: 10.15252/embr.202356937

Stephenson, S.-A. et al. Anti-tumour effects of antibodies targeting the extracellular cysteine-rich region of the receptor tyrosine kinase EphB4. Oncotarget 6, 7554–7569 (2015).

pubmed: 25831049 pmcid: 4480699 doi: 10.18632/oncotarget.3199

Ma, E. S. K. Recurrent cytogenetic abnormalities in non-Hodgkin’s lymphoma and chronic lymphocytic leukemia. Methods Mol. Biol. 1541, 279–293 (2017).

pubmed: 27910030 doi: 10.1007/978-1-4939-6703-2_22

Weiss, J. B. et al. Anaplastic lymphoma kinase and leukocyte tyrosine kinase: functions and genetic interactions in learning, memory and adult neurogenesis. Pharm. Biochem. Behav. 100, 566–574 (2012).

doi: 10.1016/j.pbb.2011.10.024

Bilsland, J. G. et al. Behavioral and neurochemical alterations in mice deficient in anaplastic lymphoma kinase suggest therapeutic potential for psychiatric indications. Neuropsychopharmacology 33, 685–700 (2008).

pubmed: 17487225 doi: 10.1038/sj.npp.1301446

Reshetnyak, A. V. et al. Augmentor α and β (FAM150) are ligands of the receptor tyrosine kinases ALK and LTK: Hierarchy and specificity of ligand-receptor interactions. Proc. Natl Acad. Sci. USA 112, 15862–15867 (2015).

pubmed: 26630010 pmcid: 4702955 doi: 10.1073/pnas.1520099112

Guan, J. et al. FAM150A and FAM150B are activating ligands for anaplastic lymphoma kinase. Elife 4 (2015).

Mo, E. S., Cheng, Q., Reshetnyak, A. V., Schlessinger, J. & Nicoli, S. Alk and Ltk ligands are essential for iridophore development in zebrafish mediated by the receptor tyrosine kinase Ltk. Proc. Natl Acad. Sci. USA 114, 12027–12032 (2017).

pubmed: 29078341 pmcid: 5692561 doi: 10.1073/pnas.1710254114

Roll, J. D. & Reuther, G. W. ALK-activating homologous mutations in LTK induce cellular transformation. PLoS One 7 (2012).

Chen, Y. et al. Oncogenic mutations of ALK kinase in neuroblastoma. Nature 455, 971–974 (2008).

pubmed: 18923524 doi: 10.1038/nature07399

George, R. E. et al. Activating mutations in ALK provide a therapeutic target in neuroblastoma. Nature 455, 975–978 (2008).

pubmed: 18923525 pmcid: 2587486 doi: 10.1038/nature07397

Wulf, A. M., Moreno, M. M., Paka, C., Rampasekova, A. & Liu, K. J. Defining pathological activities of ALK in neuroblastoma, a neural crest-derived cancer. Int. J. Mol. Sci. 22 (2021).

Mazot, P. et al. The constitutive activity of the ALK mutated at positions F1174 or R1275 impairs receptor trafficking. Oncogene 30, 2017–2025 (2011).

pubmed: 21242967 doi: 10.1038/onc.2010.595

Birchmeier, C., Sharma, S. & Wigler, M. Expression and rearrangement of the ROS1 gene in human glioblastoma cells. Proc. Natl Acad. Sci. USA 84, 9270–9274 (1987).

pubmed: 2827175 pmcid: 299735 doi: 10.1073/pnas.84.24.9270

Zhu, Q., Zhan, P., Zhang, X., Lv, T. & Song, Y. Clinicopathologic characteristics of patients with ROS1 fusion gene in non-small cell lung cancer: a meta-analysis. Transl. Lung Cancer Res. 4, 300–309 (2015).

pubmed: 26207220 pmcid: 4483477

Cai, W. et al. ROS1 fusions in Chinese patients with non-small-cell lung cancer. Ann. Oncol. 24, 1822–1827 (2013).

pubmed: 23514723 doi: 10.1093/annonc/mdt071

Zhang, Y. et al. Disease progression patterns and molecular resistance mechanisms to crizotinib of lung adenocarcinoma harboring ROS1 rearrangements. NPJ Precis. Oncol. 6 (2022).

Rikova, K. et al. Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell 131, 1190–1203 (2007).

pubmed: 18083107 doi: 10.1016/j.cell.2007.11.025

Takeuchi, K. et al. RET, ROS1 and ALK fusions in lung cancer. Nat. Med. 18, 378–381 (2012).

pubmed: 22327623 doi: 10.1038/nm.2658

Davies, K. D. & Doebele, R. C. Molecular pathways: ROS1 fusion proteins in cancer. Clin. Cancer Res. 19, 4040–4045 (2013).

pubmed: 23719267 pmcid: 3732549 doi: 10.1158/1078-0432.CCR-12-2851

Gu, T.-L. et al. Survey of tyrosine kinase signaling reveals ROS kinase fusions in human cholangiocarcinoma. PLoS One 6, 1–9 (2011).

Yu, Z.-Q. et al. ROS1-positive non-small cell lung cancer (NSCLC): biology, diagnostics, therapeutics and resistance. J. Drug Target 30, 845–857 (2022).

pubmed: 35658765 doi: 10.1080/1061186X.2022.2085730

Duma, N., Santana-Davila, R. & Molina, J. R. Non-small cell lung cancer: epidemiology, screening, diagnosis, and treatment. Mayo Clin. Proc. 94, 1623–1640 (2019).

pubmed: 31378236 doi: 10.1016/j.mayocp.2019.01.013

El-Deeb, I. M., Yoo, K. H. & Lee, S. H. ROS receptor tyrosine kinase: a new potential target for anticancer drugs. Med Res. Rev. 31, 794–818 (2011).

pubmed: 20687158

Lin, J. J. et al. Spectrum of mechanisms of resistance to crizotinib and lorlatinib in ROS1 fusion-positive lung cancer. Clin. Cancer Res. 27, 2899–2909 (2021).

pubmed: 33685866 pmcid: 8127383 doi: 10.1158/1078-0432.CCR-21-0032

Almquist, D. & Ernani, V. The road less traveled: a guide to metastatic ROS1-rearranged non-small-cell lung cancer. JCO Oncol. Pract. 17, 7–14 (2021).

pubmed: 33211628 doi: 10.1200/OP.20.00819

Gendarme, S., Bylicki, O., Chouaid, C. & Guisier, F. ROS-1 fusions in non-small-cell lung cancer: evidence to date. Curr. Oncol. 29, 641–658 (2022).

pubmed: 35200557 pmcid: 8870726 doi: 10.3390/curroncol29020057

D’Angelo, A. et al. Focus on ROS1-positive non-small cell lung cancer (NSCLC): crizotinib, resistance mechanisms and the newer generation of targeted therapies. Cancers 12, (2020).

Blume-Jensen, P. & Hunter, T. Oncogenic kinase signalling. Nature 411, 355–365 (2001).

pubmed: 11357143 doi: 10.1038/35077225

Rimkunas, V. M. et al. Analysis of receptor tyrosine kinase ROS1-positive tumors in non-small cell lung cancer: identification of a FIG-ROS1 fusion. Clin. Cancer Res. 18, 4449–4457 (2012).

pubmed: 22661537 doi: 10.1158/1078-0432.CCR-11-3351

Cheng, Y., Sun, Y., Wang, L.-Z., Yu, Y.-C. & Ding, X. Cytoplasmic c-ros oncogene 1 receptor tyrosine kinase expression may be associated with the development of human oral squamous cell carcinoma. Oncol. Lett. 10, 934–940 (2015).

pubmed: 26622599 pmcid: 4509419 doi: 10.3892/ol.2015.3340

Jóri, B. et al. Acquired G2032R resistance mutation in ROS1 to lorlatinib therapy detected with liquid biopsy. Curr. Oncol. 29, 6628–6634 (2022).

pubmed: 36135089 pmcid: 9497554 doi: 10.3390/curroncol29090520

Wirth, L. J. et al. LIBRETTO-531: a phase III study of selpercatinib in multikinase inhibitor-naïve RET-mutant medullary thyroid cancer. Future Oncol. 18, 3143–3150 (2022).

pubmed: 35969032 pmcid: 10652291 doi: 10.2217/fon-2022-0657

Li, A. Y. et al. RET fusions in solid tumors. Cancer Treat. Rev. 81, 1–11 (2019).

doi: 10.1016/j.ctrv.2019.101911

Drilon, A., Hu, Z. I., Lai, G. G. Y. & Tan, D. S. W. Targeting RET-driven cancers: lessons from evolving preclinical and clinical landscapes. Nat. Rev. Clin. Oncol. 15, 151–167 (2018).

pubmed: 29134959 doi: 10.1038/nrclinonc.2017.175

Mulligan, L. M. GDNF and the RET receptor in cancer: new insights and therapeutic potential. Front. Physiol. 9 (2018).

Liang, J. et al. Genetic landscape of papillary thyroid carcinoma in the Chinese population. J. Pathol. 244, 215–226 (2018).

pubmed: 29144541 doi: 10.1002/path.5005

Romei, C., Ciampi, R. & Elisei, R. A comprehensive overview of the role of the RET proto-oncogene in thyroid carcinoma. Nat. Rev. Endocrinol. 12, 192–202 (2016).

pubmed: 26868437 doi: 10.1038/nrendo.2016.11

Takahashi, M. RET receptor signaling: function in development, metabolic disease, and cancer. Proc. Jpn Acad. Ser. B Phys. Biol. Sci. 98, 112–125 (2022).

pubmed: 35283407 pmcid: 8948417 doi: 10.2183/pjab.98.008

Chi, X. et al. Ret-dependent cell rearrangements in the Wolffian duct epithelium initiate ureteric bud morphogenesis. Dev. Cell 17, 199–209 (2009).

pubmed: 19686681 pmcid: 2762206 doi: 10.1016/j.devcel.2009.07.013

Enomoto, H. et al. RET signaling is essential for migration, axonal growth and axon guidance of developing sympathetic neurons. Development 128, 3963–3974 (2001).

pubmed: 11641220 doi: 10.1242/dev.128.20.3963

Schuchardt, A., D’Agati, V., Larsson-Blomberg, L., Costantini, F. & Pachnis, V. Defects in the kidney and enteric nervous system of mice lacking the tyrosine kinase receptor Ret. Nature 367, 380–383 (1994).

pubmed: 8114940 doi: 10.1038/367380a0

Tomuschat, C. & Puri, P. RET gene is a major risk factor for Hirschsprung’s disease: a meta-analysis. Pediatr. Surg. Int. 31, 701–710 (2015).

pubmed: 26164711 doi: 10.1007/s00383-015-3731-y

Jain, S. et al. Mice expressing a dominant-negative Ret mutation phenocopy human Hirschsprung disease and delineate a direct role of Ret in spermatogenesis. Development 131, 5503–5513 (2004).

pubmed: 15469971 doi: 10.1242/dev.01421

Smith, D. P., Houghton, C. & Ponder, B. A. Germline mutation of RET codon 883 in two cases of de novo MEN 2B. Oncogene 15, 1213–1217 (1997).

pubmed: 9294615 doi: 10.1038/sj.onc.1201481

Mulligan, L. M. et al. Germ-line mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A. Nature 363, 458–460 (1993).

pubmed: 8099202 doi: 10.1038/363458a0

Wagner, S. M., Zhu, S., Nicolescu, A. C. & Mulligan, L. M. Molecular mechanisms of RET receptor-mediated oncogenesis in multiple endocrine neoplasia 2. Clinics 67, 77–84 (2012).

pubmed: 22584710 pmcid: 3328826 doi: 10.6061/clinics/2012(Sup01)14

Li, Q., Tie, Y., Alu, A., Ma, X. & Shi, H. Targeted therapy for head and neck cancer: signaling pathways and clinical studies. Signal Transduct. Target Ther 8, 1–28 (2023).

Perrinjaquet, M., Vilar, M. & Ibáñez, C. F. Protein-tyrosine phosphatase SHP2 contributes to GDNF neurotrophic activity through direct binding to phospho-Tyr687 in the RET receptor tyrosine kinase. J. Biol. Chem. 285, 31867–31875 (2010).

pubmed: 20682772 pmcid: 2951258 doi: 10.1074/jbc.M110.144923

Schuringa, J. J. et al. MEN2A-RET-induced cellular transformation by activation of STAT3. Oncogene 20, 5350–5358 (2001).

pubmed: 11536047 doi: 10.1038/sj.onc.1204715

Kawamoto, Y. et al. Identification of RET autophosphorylation sites by mass spectrometry. J. Biol. Chem. 279, 14213–14224 (2004).

pubmed: 14711813 doi: 10.1074/jbc.M312600200

Iwashita, T., Asai, N., Murakami, H., Matsuyama, M. & Takahashi, M. Identification of tyrosine residues that are essential for transforming activity of the ret proto-oncogene with MEN2A or MEN2B mutation. Oncogene 12, 481–487 (1996).

pubmed: 8637703

Encinas, M., Crowder, R. J., Milbrandt, J. & Johnson, E. M. Tyrosine 981, a novel ret autophosphorylation site, binds c-Src to mediate neuronal survival. J. Biol. Chem. 279, 18262–18269 (2004).

pubmed: 14766744 doi: 10.1074/jbc.M400505200

Borrello, M. G. et al. The full oncogenic activity of Ret/ptc2 depends on tyrosine 539, a docking site for phospholipase Cgamma. Mol. Cell Biol. 16, 2151–2163 (1996).

pubmed: 8628282 pmcid: 231203 doi: 10.1128/MCB.16.5.2151

Asai, N., Murakami, H., Iwashita, T. & Takahashi, M. A mutation at tyrosine 1062 in MEN2A-Ret and MEN2B-Ret impairs their transforming activity and association with shc adaptor proteins. J. Biol. Chem. 271, 17644–17649 (1996).

pubmed: 8663426 doi: 10.1074/jbc.271.30.17644

Alberti, L. et al. Grb2 binding to the different isoforms of Ret tyrosine kinase. Oncogene 17, 1079–1087 (1998).

pubmed: 9764818 doi: 10.1038/sj.onc.1202046

Liu, X. et al. Oncogenic RET receptors display different autophosphorylation sites and substrate binding specificities. J. Biol. Chem. 271, 5309–5312 (1996).

pubmed: 8621380 doi: 10.1074/jbc.271.10.5309

Gujral, T. S., Singh, V. K., Jia, Z. & Mulligan, L. M. Molecular mechanisms of RET receptor-mediated oncogenesis in multiple endocrine neoplasia 2B. Cancer Res. 66, 10741–10749 (2006).

pubmed: 17108110 doi: 10.1158/0008-5472.CAN-06-3329

Liu, X., Shen, T., Mooers, B. H. M., Hilberg, F. & Wu, J. Drug resistance profiles of mutations in the RET kinase domain. Br. J. Pharm. 175, 3504–3515 (2018).

doi: 10.1111/bph.14395

Carlomagno, F. et al. Disease associated mutations at valine 804 in the RET receptor tyrosine kinase confer resistance to selective kinase inhibitors. Oncogene 23, 6056–6063 (2004).

pubmed: 15184865 doi: 10.1038/sj.onc.1207810

Mulligan, L. M. RET revisited: expanding the oncogenic portfolio. Nat. Rev. Cancer 14, 173–186 (2014).

pubmed: 24561444 doi: 10.1038/nrc3680

De Falco, V. et al. Ponatinib (AP24534) is a novel potent inhibitor of oncogenic RET mutants associated with thyroid cancer. J. Clin. Endocrinol. Metab. 98, 811–819 (2013).

doi: 10.1210/jc.2012-2672

Kato, S. et al. RET aberrations in diverse cancers: next-generation sequencing of 4,871 patients. Clin. Cancer Res. 23, 1988–1997 (2017).

pubmed: 27683183 doi: 10.1158/1078-0432.CCR-16-1679

Iwashita, T. et al. A two-hit model for development of multiple endocrine neoplasia type 2B by RET mutations. Biochem. Biophys. Res. Commun. 268, 804–808 (2000).

pubmed: 10679286 doi: 10.1006/bbrc.2000.2227

Muzza, M. et al. Four novel RET germline variants in exons 8 and 11 display an oncogenic potential in vitro. Eur. J. Endocrinol. 162, 771–777 (2010).

pubmed: 20103606 doi: 10.1530/EJE-09-0929

Meng, S., Wu, H., Wang, J. & Qiu, Q. Systematic analysis of tyrosine kinase inhibitor response to RET gatekeeper mutations in thyroid cancer. Mol. Inf. 35, 495–505 (2016).

doi: 10.1002/minf.201600039

Stricker, S., Rauschenberger, V. & Schambony, A. ROR-family receptor tyrosine kinases. Curr. Top. Dev. Biol. 123, 105–142 (2017).

pubmed: 28236965 doi: 10.1016/bs.ctdb.2016.09.003

Masiakowski, P. & Carroll, R. D. A novel family of cell surface receptors with tyrosine kinase-like domain. J. Biol. Chem. 267, 26181–26190 (1992).

pubmed: 1334494 doi: 10.1016/S0021-9258(18)35733-8

Daneshmanesh, A. H. et al. Ror1, a cell surface receptor tyrosine kinase is expressed in chronic lymphocytic leukemia and may serve as a putative target for therapy. Int. J. Cancer 123, 1190–1195 (2008).

pubmed: 18546292 doi: 10.1002/ijc.23587

Baskar, S. et al. Unique cell surface expression of receptor tyrosine kinase ROR1 in human B-cell chronic lymphocytic leukemia. Clin. Cancer Res. 14, 396–404 (2008).

pubmed: 18223214 doi: 10.1158/1078-0432.CCR-07-1823

Cui, B. et al. High-level ROR1 associates with accelerated disease progression in chronic lymphocytic leukemia. Blood 128, 2931–2940 (2016).

pubmed: 27815263 pmcid: 5179332 doi: 10.1182/blood-2016-04-712562

Choudhury, A. et al. Silencing of ROR1 and FMOD with siRNA results in apoptosis of CLL cells. Br. J. Haematol. 151, 327–335 (2010).

pubmed: 20813009 doi: 10.1111/j.1365-2141.2010.08362.x

Zhao, Y. et al. Tyrosine kinase ROR1 as a target for anti-cancer therapies. Front. Oncol. 11 (2021).

Sánchez-Solana, B., Laborda, J. & Baladrón, V. Mouse resistin modulates adipogenesis and glucose uptake in 3T3-L1 preadipocytes through the ROR1 receptor. Mol. Endocrinol. 26, 110–127 (2012).

pubmed: 22074948 doi: 10.1210/me.2011-1027

Kurita, Y. et al. A high-fat/high-sucrose diet induces WNT4 expression in mouse pancreatic β-cells. Kurum. Med. J. 65, 55–62 (2019).

doi: 10.2739/kurumemedj.MS652008

Heliste, J. et al. Receptor tyrosine kinase profiling of ischemic heart identifies ROR1 as a potential therapeutic target. BMC Cardiovasc. Disord. 18, (2018).

Gui, B. et al. Heterozygous recurrent mutations inducing dysfunction of ROR2 gene in patients with short stature. Front. Cell Dev. Biol. 9 (2021).

Zisch, A. H. & Pasquale, E. B. The Eph family: a multitude of receptors that mediate cell recognition signals. Cell Tissue Res. 290, 217–226 (1997).

pubmed: 9321683 doi: 10.1007/s004410050926

Eph Nomenclature Committee. Unified nomenclature for Eph family receptors and their ligands, the ephrins. Eph Nomenclature Committee. Cell 90, 403–404 (1997).

doi: 10.1016/S0092-8674(00)80500-0

Davy, A. & Soriano, P. Ephrin signaling in vivo: look both ways. Dev. Dyn. 232, 1–10 (2005).

pubmed: 15580616 doi: 10.1002/dvdy.20200

Rohani, N., Canty, L., Luu, O., Fagotto, F. & Winklbauer, R. EphrinB/EphB signaling controls embryonic germ layer separation by contact-induced cell detachment. PLoS Biol. 9 (2011).

Kuijper, S., Turner, C. J. & Adams, R. H. Regulation of angiogenesis by Eph-ephrin interactions. Trends Cardiovasc. Med. 17, 145–151 (2007).

pubmed: 17574121 doi: 10.1016/j.tcm.2007.03.003

Genander, M. & Frisén, J. Ephrins and Eph receptors in stem cells and cancer. Curr. Opin. Cell Biol. 22, 611–616 (2010).

pubmed: 20810264 doi: 10.1016/j.ceb.2010.08.005

Arora, S., Scott, A. M. & Janes, P. W. Eph receptors in cancer. Biomedicines 11 (2023).

Giaginis, C. et al. Clinical significance of ephrin (eph)-A1, -A2, -a4, -a5 and -a7 receptors in pancreatic ductal adenocarcinoma. Pathol. Oncol. Res. 16, 267–276 (2010).

pubmed: 19949912 doi: 10.1007/s12253-009-9221-6

Kandouz, M. The Eph/Ephrin family in cancer metastasis: communication at the service of invasion. Cancer Metastasis Rev. 31, 353–373 (2012).

pubmed: 22549394 doi: 10.1007/s10555-012-9352-1

Lisabeth, E. M., Fernandez, C. & Pasquale, E. B. Cancer somatic mutations disrupt functions of the EphA3 receptor tyrosine kinase through multiple mechanisms. Biochemistry 51, 1464–1475 (2012).

pubmed: 22242939 doi: 10.1021/bi2014079

Lisabeth, E. M., Falivelli, G. & Pasquale, E. B. Eph receptor signaling and ephrins. Cold Spring Harb. Perspect. Biol. 5, 1–20 (2013).

doi: 10.1101/cshperspect.a009159

Ferguson, B. D. et al. Novel EPHB4 receptor tyrosine kinase mutations and kinomic pathway analysis in lung cancer. Sci. Rep. 5 (2015).

Chakraborty, S., Baruah, R., Mishra, N. & Varma, A. K. In-silico and structure-based assessment to evaluate pathogenicity of missense mutations associated with non-small cell lung cancer identified in the Eph-ephrin class of proteins. Genom. Inform. 21 (2023).

Faoro, L. et al. EphA2 mutation in lung squamous cell carcinoma promotes increased cell survival, cell invasion, focal adhesions, and mammalian target of rapamycin activation. J. Biol. Chem. 285, 18575–18585 (2010).

pubmed: 20360610 pmcid: 2881783 doi: 10.1074/jbc.M109.075085

Zhuang, G. et al. Effects of cancer-associated EPHA3 mutations on lung cancer. J. Natl Cancer Inst. 104, 1182–1197 (2012).

pubmed: 22829656 doi: 10.1093/jnci/djs297

Magnus, J. H., Husby, G. & Kolset, S. O. Presence of glycosaminoglycans in purified AA type amyloid fibrils associated with juvenile rheumatoid arthritis. Ann. Rheum. Dis. 48, 215–219 (1989).

pubmed: 2930277 pmcid: 1003724 doi: 10.1136/ard.48.3.215

Kim, G.-H., Her, J.-H. & Han, J.-K. Ryk cooperates with Frizzled 7 to promote Wnt11-mediated endocytosis and is essential for Xenopus laevis convergent extension movements. J. Cell Biol. 182, 1073–1082 (2008).

pubmed: 18809723 pmcid: 2542470 doi: 10.1083/jcb.200710188

Halford, M. M. et al. Ryk-deficient mice exhibit craniofacial defects associated with perturbed Eph receptor crosstalk. Nat. Genet. 25, 414–418 (2000).

pubmed: 10932185 doi: 10.1038/78099

Roy, J. P., Halford, M. M. & Stacker, S. A. The biochemistry, signalling and disease relevance of RYK and other WNT-binding receptor tyrosine kinases. Growth Factors 36, 15–40 (2018).

pubmed: 29806777 doi: 10.1080/08977194.2018.1472089

Green, J., Nusse, R. & van Amerongen, R. The role of Ryk and Ror receptor tyrosine kinases in Wnt signal transduction. Cold Spring Harb. Perspect. Biol. 6, 9175–9175 (2014).

doi: 10.1101/cshperspect.a009175

Fradkin, L. G., Dura, J.-M. & Noordermeer, J. N. Ryks: new partners for Wnts in the developing and regenerating nervous system. Trends Neurosci. 33, 84–92 (2010).

pubmed: 20004982 doi: 10.1016/j.tins.2009.11.005

Schmitt, A. M. et al. Wnt-Ryk signalling mediates medial-lateral retinotectal topographic mapping. Nature 439, 31–37 (2006).

pubmed: 16280981 doi: 10.1038/nature04334

Lu, W., Yamamoto, V., Ortega, B. & Baltimore, D. Mammalian Ryk is a Wnt coreceptor required for stimulation of neurite outgrowth. Cell 119, 97–108 (2004).

pubmed: 15454084 doi: 10.1016/j.cell.2004.09.019

Macheda, M. L. et al. The Wnt receptor Ryk plays a role in mammalian planar cell polarity signaling. J. Biol. Chem. 287, 29312–29323 (2012).

pubmed: 22773843 pmcid: 3436188 doi: 10.1074/jbc.M112.362681

Andre, P. et al. The Wnt coreceptor Ryk regulates Wnt/planar cell polarity by modulating the degradation of the core planar cell polarity component Vangl2. J. Biol. Chem. 287, 44518–44525 (2012).

pubmed: 23144463 pmcid: 3531765 doi: 10.1074/jbc.M112.414441

Famili, F. et al. The non-canonical Wnt receptor Ryk regulates hematopoietic stem cell repopulation in part by controlling proliferation and apoptosis. Cell Death Dis. 7, (2016).

Jeong, S.-Y., Lyu, J., Kim, J.-A. & Oh, I.-H. Ryk modulates the niche activity of mesenchymal stromal cells by fine-tuning canonical Wnt signaling. Exp. Mol. Med. 52, 1140–1151 (2020).

pubmed: 32724069 pmcid: 8080773 doi: 10.1038/s12276-020-0477-y

Kikuchi, A., Yamamoto, H., Sato, A. & Matsumoto, S. New insights into the mechanism of wnt signaling pathway activation. in International Review of Cell and Molecular Biology (ed Kwang, W. J.) Vol. 291, 21–71 (Academic Press, 2011).

Zhu, N. et al. Challenging role of Wnt5a and its signaling pathway in cancer metastasis (Review). Exp. Ther. Med. 8, 3–8 (2014).

pubmed: 24944588 pmcid: 4061222 doi: 10.3892/etm.2014.1676

Ford, C. E., Qian Ma, S. S., Quadir, A. & Ward, R. L. The dual role of the novel Wnt receptor tyrosine kinase, ROR2, in human carcinogenesis. Int. J. Cancer 133, 779–787 (2013).

pubmed: 23233346 doi: 10.1002/ijc.27984

Katso, R. M. et al. Overexpression of H-Ryk in epithelial ovarian cancer: prognostic significance of receptor expression. Clin. Cancer Res. 6, 3271–3281 (2000).

pubmed: 10955813

Mossie, K. et al. Colon carcinoma kinase-4 defines a new subclass of the receptor tyrosine kinase family. Oncogene 11, 2179–2184 (1995).

pubmed: 7478540

Berger, H., Wodarz, A. & Borchers, A. PTK7 Faces the Wnt in development and disease. Front. Cell Dev. Biol. 5 (2017).

Lee, H. K., Chauhan, S. K., Kay, E. & Dana, R. Flt-1 regulates vascular endothelial cell migration via a protein tyrosine kinase-7-dependent pathway. Blood 117, 5762–5771 (2011).

pubmed: 21460247 pmcid: 3110033 doi: 10.1182/blood-2010-09-306928

Lander, R. & Petersen, C. P. Wnt, Ptk7, and FGFRL expression gradients control trunk positional identity in planarian regeneration. Elife 5 (2016).

Dunn, N. R. & Tolwinski, N. S. Ptk7 and Mcc, unfancied components in non-canonical Wnt signaling and cancer. Cancers 8 (2016).

Grimes, D. T. et al. Zebrafish models of idiopathic scoliosis link cerebrospinal fluid flow defects to spine curvature. Science 352, 1341–1344 (2016).

pubmed: 27284198 pmcid: 5574193 doi: 10.1126/science.aaf6419

Wang, M. et al. Role of the planar cell polarity gene Protein tyrosine kinase 7 in neural tube defects in humans. Birth Defects Res. A Clin. Mol. Teratol. 103, 1021–1027 (2015).

pubmed: 26368655 doi: 10.1002/bdra.23422

Lu, X. et al. PTK7/CCK-4 is a novel regulator of planar cell polarity in vertebrates. Nature 430, 93–98 (2004).

pubmed: 15229603 doi: 10.1038/nature02677

Chen, R. et al. A meta-analysis of lung cancer gene expression identifies PTK7 as a survival gene in lung adenocarcinoma. Cancer Res. 74, 2892–2902 (2014).

pubmed: 24654231 pmcid: 4084668 doi: 10.1158/0008-5472.CAN-13-2775

Jin, J., Ryu, H. S., Lee, K. B. & Jang, J.-J. High expression of protein tyrosine kinase 7 significantly associates with invasiveness and poor prognosis in intrahepatic cholangiocarcinoma. PLoS One 9, 1–11 (2014).

Lhoumeau, A.-C. et al. Overexpression of the promigratory and prometastatic PTK7 receptor is associated with an adverse clinical outcome in colorectal cancer. PLoS One, 10 (2015).

Wang, H. et al. PTK7 protein is decreased in epithelial ovarian carcinomas with poor prognosis. Int. J. Clin. Exp. Pathol. 7, 7881–7889 (2014).

pubmed: 25550828 pmcid: 4270512

Jiang, W. et al. PTK7 expression is associated with lymph node metastasis, ALK and EGFR mutations in lung adenocarcinomas. Histol. Histopathol. 35, 489–495 (2020).

pubmed: 31701509

Gärtner, S. et al. PTK 7 Is a transforming gene and prognostic marker for breast cancer and nodal metastasis involvement. PLoS One 9, 1–11 (2014).

doi: 10.1371/journal.pone.0084472

Damelin, M. et al. A PTK7-targeted antibody-drug conjugate reduces tumor-initiating cells and induces sustained tumor regressions. Sci. Transl. Med. 9 (2017).

Jung, P. et al. Isolation of human colon stem cells using surface expression of PTK7. Stem Cell Rep. 5, 979–987 (2015).

doi: 10.1016/j.stemcr.2015.10.003

Herrmann, J. L. et al. Mediation of NGF-stimulated extracellular matrix invasion by the human melanoma low-affinity p75 neurotrophin receptor: melanoma p75 functions independently of trkA. Mol. Biol. Cell 4, 1205–1216 (1993).

pubmed: 8305739 pmcid: 275754 doi: 10.1091/mbc.4.11.1205

Mahendram, S., Subapanditha, M. K., McFarlane, N., Venugopal, C. & Singh, S. K. Flow-cytometric identification and characterization of neural brain tumor-initiating cells for pathophysiological study and biomedical applications. in Neural Surface Antigens 199–211 (Elsevier, 2015). https://doi.org/10.1016/B978-0-12-800781-5.00017-7 .

Chao, M. V. et al. Structure and functions of NGF receptors. in Botulinum and Tetanus Neurotoxins 17–24 (Springer US, Boston, MA, 1993). https://doi.org/10.1007/978-1-4757-9542-4_3 .

Wu, R., Li, K., Yuan, M. & Luo, K. Q. Nerve growth factor receptor increases the tumor growth and metastatic potential of triple-negative breast cancer cells. Oncogene 40, 2165–2181 (2021).

pubmed: 33627781 doi: 10.1038/s41388-021-01691-y

Wang, G. et al. Rational design and crystallographic analysis of novel isoform-selective TRKA inhibitors for cancer therapy. Acta Pharm. Sin. B 13, 440–443 (2023).

pubmed: 36815052 doi: 10.1016/j.apsb.2022.10.012

Regua, A. T., Doheny, D., Arrigo, A. & Lo, H.-W. Trk receptor tyrosine kinases in metastasis and cancer therapy. Discov. Med. 28, 195–203 (2019).

pubmed: 31928627

Okimoto, R. A. & Bivona, T. G. AXL receptor tyrosine kinase as a therapeutic target in NSCLC. Lung Cancer 6, 27–34 (2015).

pubmed: 28210148 pmcid: 5217513

Falcone, I. et al. AXL Receptor in breast cancer: molecular involvement and therapeutic limitations. Int. J. Mol. Sci. 21 (2020).

Graham, D. K., DeRyckere, D., Davies, K. D. & Earp, H. S. The TAM family: phosphatidylserine sensing receptor tyrosine kinases gone awry in cancer. Nat. Rev. Cancer 14, 769–785 (2014).

pubmed: 25568918 doi: 10.1038/nrc3847

Linger, R. M. A., Keating, A. K., Earp, H. S. & Graham, D. K. TAM receptor tyrosine kinases: biologic functions, signaling, and potential therapeutic targeting in human cancer. Adv. Cancer Res. 100, 35–83 (2008).

pubmed: 18620092 pmcid: 3133732 doi: 10.1016/S0065-230X(08)00002-X

Gay, C. M., Balaji, K. & Byers, L. A. Giving AXL the axe: targeting AXL in human malignancy. Br. J. Cancer 116, 415–423 (2017).

pubmed: 28072762 pmcid: 5318970 doi: 10.1038/bjc.2016.428

Mudduluru, G., Vajkoczy, P. & Allgayer, H. Myeloid zinc finger 1 induces migration, invasion, and in vivo metastasis through Axl gene expression in solid cancer. Mol. Cancer Res. 8, 159–169 (2010).

pubmed: 20145042 doi: 10.1158/1541-7786.MCR-09-0326

Mudduluru, G., Leupold, J. H., Stroebel, P. & Allgayer, H. PMA up-regulates the transcription of Axl by AP-1 transcription factor binding to TRE sequences via the MAPK cascade in leukaemia cells. Biol. Cell 103, 21–33 (2011).

doi: 10.1042/BC20100094

Rankin, E. B. et al. Direct regulation of GAS6/AXL signaling by HIF promotes renal metastasis through SRC and MET. Proc. Natl Acad. Sci. USA 111, 13373–13378 (2014).

pubmed: 25187556 pmcid: 4169907 doi: 10.1073/pnas.1404848111

Zhang, Y., Earp, H. S. & Liu, P. Beyond growth signaling: apoptotic sensor MERTK activates AKT by a novel mechanism. Mol. Cell Oncol. 6 (2019).

Jiang, Y. et al. MERTK mediated novel site Akt phosphorylation alleviates SAV1 suppression. Nat. Commun. 10 (2019).

Zhu, C., Wei, Y. & Wei, X. AXL receptor tyrosine kinase as a promising anti-cancer approach: functions, molecular mechanisms and clinical applications. Mol. Cancer 18 (2019).

Rankin, E. & Giaccia, A. The receptor tyrosine kinase AXL in cancer progression. Cancers 8 (2016).

Mudduluru, G. & Allgayer, H. The human receptor tyrosine kinase Axl gene—promoter characterization and regulation of constitutive expression by Sp1, Sp3 and CpG methylation. Biosci. Rep. 28, 161–176 (2008).

pubmed: 18522535 doi: 10.1042/BSR20080046

Zhai, X. et al. Gas6/AXL pathway: immunological landscape and therapeutic potential. Front. Oncol. 13 (2023).

Salian-Mehta, S. et al. Functional consequences of AXL sequence variants in hypogonadotropic hypogonadism. J. Clin. Endocrinol. Metab. 99, 1452–1460 (2014).

pubmed: 24476074 pmcid: 3973777 doi: 10.1210/jc.2013-3426

Dilara Fatma, A. & Özkan, D. Molecular profiling of TAM tyrosine kinase receptors and ligands in endometrial carcinoma: An in silico-study. Taiwan J. Obstet. Gynecol. 62, 311–324 (2023).

doi: 10.1016/j.tjog.2022.09.010

Szklarczyk, D. et al. STRING v11: protein–protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res. 47, 607–613 (2019).

doi: 10.1093/nar/gky1131

Sensi, M. et al. Human cutaneous melanomas lacking MITF and melanocyte differentiation antigens express a functional Axl receptor kinase. J. Investig. Dermatol 131, 2448–2457 (2011).

pubmed: 21796150 doi: 10.1038/jid.2011.218

Al Kafri, N. & Hafizi, S. Identification of signalling pathways activated by Tyro3 that promote cell survival, proliferation and invasiveness in human cancer cells. Biochem. Biophys. Rep. 28 (2021).

Al Kafri, N. & Hafizi, S. Tumour-secreted protein S (ProS1) activates a tyro3-Erk signalling axis and protects cancer cells from apoptosis. Cancers 11 (2019).

Smart, S. K., Vasileiadi, E., Wang, X., DeRyckere, D. & Graham, D. K. The emerging role of TYRO3 as a therapeutic target in cancer. Cancers (Basel) 10, 1–27 (2018).

Seshagiri, S. et al. Recurrent R-spondin fusions in colon cancer. Nature 488, 660–664 (2012).

pubmed: 22895193 pmcid: 3690621 doi: 10.1038/nature11282

Ding, L. et al. Somatic mutations affect key pathways in lung adenocarcinoma. Nature 455, 1069–1075 (2008).

pubmed: 18948947 pmcid: 2694412 doi: 10.1038/nature07423

Wagle, N. et al. MAP kinase pathway alterations in BRAF-mutant melanoma patients with acquired resistance to combined RAF/MEK inhibition. Cancer Discov. 4, 61–68 (2014).

pubmed: 24265154 doi: 10.1158/2159-8290.CD-13-0631

Loriaux, M. M. et al. High-throughput sequence analysis of the tyrosine kinome in acute myeloid leukemia. Blood 111, 4788–4796 (2008).

pubmed: 18252861 pmcid: 2343606 doi: 10.1182/blood-2007-07-101394

Jiao, Y. et al. Whole‐exome sequencing of pancreatic neoplasms with acinar differentiation. J. Pathol. 232, 428–435 (2014).

pubmed: 24293293 pmcid: 4048021 doi: 10.1002/path.4310

Easty, D. J. et al. Novel and known protein tyrosine kinases and their abnormal expression in human melanoma. J. Investig. Dermatol 101, 679–684 (1993).

pubmed: 8228328 doi: 10.1111/1523-1747.ep12371675

Krauthammer, M. et al. Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma. Nat. Genet. 44, 1006–1014 (2012).

pubmed: 22842228 pmcid: 3432702 doi: 10.1038/ng.2359

Shi, C. et al. The proto-oncogene Mer tyrosine kinase is a novel therapeutic target in mantle cell lymphoma. J. Hematol. Oncol. 11 (2018).

Lee-Sherick, A. B. et al. MERTK inhibition alters the PD-1 axis and promotes anti-leukemia immunity. JCI Insight 3, 1–18 (2018).

Farnworth-McHugh, S. et al. Potential oncogenic effect of the MERTK-dependent apoptotic-cell clearance pathway in starry-sky B-cell lymphoma. Front. Immunol. 11 (2020).

Ohta, S. et al. The role of MerTK in promoting cell migration is enhanced by the oncogenic Ras/IL‐33 signaling axis. FEBS J. 289, 1950–1967 (2022).

pubmed: 34743410 doi: 10.1111/febs.16271

Yi, J. H. et al. MerTK is a novel therapeutic target in gastric cancer. Oncotarget 8, 96656–96667 (2017).

pubmed: 29228560 doi: 10.18632/oncotarget.3750

Xie, S. et al. Mer receptor tyrosine kinase is frequently overexpressed in human non-small cell lung cancer, confirming resistance to erlotinib. Oncotarget 6, 9206–9219 (2015).

pubmed: 25826078 pmcid: 4496212 doi: 10.18632/oncotarget.3280

Tworkoski, K. A. et al. MERTK controls melanoma cell migration and survival and differentially regulates cell behavior relative to AXL. Pigment Cell Melanoma Res. 26, 527–541 (2013).

pubmed: 23617806 pmcid: 3918898 doi: 10.1111/pcmr.12110

Hucthagowder, V. et al. Resequencing analysis of the human candidate ras and receptor tyrosine kinase gene family in multiple myeloma. Blood 116, 301–301 (2010).

doi: 10.1182/blood.V116.21.301.301

Audo, I. et al. MERTK mutation update in inherited retinal diseases. Hum. Mutat. 39, 887–913 (2018).

pubmed: 29659094 doi: 10.1002/humu.23431

Eklund, L., Kangas, J. & Saharinen, P. Angiopoietin-tie signalling in the cardiovascular and lymphatic systems. Clin. Sci. 131, 87–103 (2017).

doi: 10.1042/CS20160129

Puri, M. C., Partanen, J., Rossant, J. & Bernstein, A. Interaction of the TEK and TIE receptor tyrosine kinases during cardiovascular development. Development 126, 4569–4580 (1999).

pubmed: 10498691 doi: 10.1242/dev.126.20.4569

Schnürch, H. & Risau, W. Expression of tie-2, a member of a novel family of receptor tyrosine kinases, in the endothelial cell lineage. Development 119, 957–968 (1993).

pubmed: 8187650 doi: 10.1242/dev.119.3.957

Duran, C. L. et al. Targeting Tie2 in the tumor microenvironment: from angiogenesis to dissemination. Cancers. 13 (2021).

Madukwe, J. & Ferguson, K. The mechanism of ligand‐induced activation of the tie family of receptor tyrosine kinases. FASEB J. 33, 809.10–809.10 (2019).

doi: 10.1096/fasebj.2019.33.1_supplement.809.10

Monk, B. J. et al. Anti-angiopoietin therapy with trebananib for recurrent ovarian cancer (TRINOVA-1): a randomised, multicentre, double-blind, placebo-controlled phase 3 trial. Lancet Oncol. 15, 799–808 (2014).

pubmed: 24950985 doi: 10.1016/S1470-2045(14)70244-X

Monk, B. J. et al. Final results of a phase 3 study of trebananib plus weekly paclitaxel in recurrent ovarian cancer (TRINOVA-1): long-term survival, impact of ascites, and progression-free survival-2. Gynecol. Oncol. 143, 27–34 (2016).

pubmed: 27546885 doi: 10.1016/j.ygyno.2016.07.112

Campochiaro, P. A. et al. Treatment of diabetic macular edema with an inhibitor of vascular endothelial-protein tyrosine phosphatase that activates Tie2. Ophthalmology 122, 545–554 (2015).

pubmed: 25439435 doi: 10.1016/j.ophtha.2014.09.023

Ishibashi, M. et al. Tyrosine kinase receptor TIE-1 mediates platinum resistance by promoting nucleotide excision repair in ovarian cancer. Sci. Rep. 8 (2018).

Marguier, A. et al. TIE-2 signaling activation by angiopoietin 2 on myeloid-derived suppressor cells promotes melanoma-specific T-cell inhibition. Front. Immunol. 13 (2022).

Dang, N. et al. CD167 acts as a novel costimulatory receptor in T-cell activation. J. Immunother. 32, 773–784 (2009).

pubmed: 19752756 doi: 10.1097/CJI.0b013e3181acea46

Fridman, R. & Agarwal, G. New concepts on the interactions of discoidin domain receptors with collagen. Biochim. Biophys. Acta Mol. Cell Res. 1866 (2019).

Iwai, L. K., Luczynski, M. T. & Huang, P. H. Discoidin domain receptors: a proteomic portrait. Cell Mol. Life Sci. 71, 3269–3279 (2014).

pubmed: 24705941 pmcid: 11113481 doi: 10.1007/s00018-014-1616-1

Henriet, E. et al. Multitasking discoidin domain receptors are involved in several and specific hallmarks of cancer. Cell Adh. Migr. 12, 363–377 (2018).

pubmed: 29701112 pmcid: 6411096

Ford, C. E. et al. Expression and mutation analysis of the discoidin domain receptors 1 and 2 in non-small cell lung carcinoma. Br. J. Cancer 96, 808–814 (2007).

pubmed: 17299390 pmcid: 2360060 doi: 10.1038/sj.bjc.6603614

Hammerman, P. S. et al. Mutations in the DDR2 kinase gene identify a novel therapeutic target in squamous cell lung cancer. Cancer Discov. 1, 78–89 (2011).

pubmed: 22328973 pmcid: 3274752 doi: 10.1158/2159-8274.CD-11-0005

Yang, S. et al. Discoidin domain receptor 1 is associated with poor prognosis of non-small cell lung carcinomas. Oncol. Rep. 24, 311–319 (2010).

pubmed: 20596615

Yeung, D. A. et al. Clustering, spatial distribution, and phosphorylation of discoidin domain receptors 1 and 2 in response to soluble collagen I. J. Mol. Biol. 431, 368–390 (2019).

pubmed: 30458172 doi: 10.1016/j.jmb.2018.11.015

Orgel, J. P. R. O. & Madhurapantula, R. S. A structural prospective for collagen receptors such as DDR and their binding of the collagen fibril. Biochim. Biophys. Acta Mol. Cell Res. 1866 (2019).

Leitinger, B. Discoidin domain receptor functions in physiological and pathological conditions. Int. Rev. Cell Mol. Biol. 310, 39–87 (2014).

pubmed: 24725424 pmcid: 4021107 doi: 10.1016/B978-0-12-800180-6.00002-5

Majo, S. & Auguste, P. The Yin and Yang of discoidin domain receptors (DDRs): implications in tumor growth and metastasis development. Cancers (Basel) 13, 1–27 (2021).

doi: 10.3390/cancers13071725

Bonfil, R. D. et al. Expression and subcellular localization of Discoidin Domain Receptor 1 (DDR1) define prostate cancer aggressiveness. Cancer Cell Int. 21 (2021).

Fu, H.-L. et al. Shedding of discoidin domain receptor 1 by membrane-type matrix metalloproteinases. J. Biol. Chem. 288, 12114–12129 (2013).

pubmed: 23519472 pmcid: 3636896 doi: 10.1074/jbc.M112.409599

Castro-Sanchez, L., Soto-Guzman, A., Guaderrama-Diaz, M., Cortes-Reynosa, P. & Salazar, E. P. Role of DDR1 in the gelatinases secretion induced by native type IV collagen in MDA-MB-231 breast cancer cells. Clin. Exp. Metastasis 28, 463–477 (2011).

pubmed: 21461859 doi: 10.1007/s10585-011-9385-9

Le, C. C. et al. LRP-1 promotes colon cancer cell proliferation in 3D collagen matrices by mediating DDR1 endocytosis. Front. Cell Dev. Biol. 8 (2020).

Poudel, B., Lee, Y.-M. & Kim, D.-K. DDR2 inhibition reduces migration and invasion of murine metastatic melanoma cells by suppressing MMP2/9 expression through ERK/NF-κB pathway. Acta Biochim. Biophys. Sin. 47, 292–298 (2015).

pubmed: 25733533 doi: 10.1093/abbs/gmv005

Reger de Moura, C. et al. Discoidin domain receptors: a promising target in melanoma. Pigment. Cell Melanoma Res. 32, 697–707 (2019).

pubmed: 31271515 doi: 10.1111/pcmr.12809

Sugimoto, K. et al. Prognostic impact of phosphorylated discoidin domain receptor-1 in esophageal cancer. J. Surg. Res. 235, 479–486 (2019).

pubmed: 30691832 doi: 10.1016/j.jss.2018.10.032

Alexander, S. P. et al. The concise guide to PHARMACOLOGY 2015/16: catalytic receptors. Br. J. Pharm. 172, 5979–6023 (2015).

doi: 10.1111/bph.13353

Raghunath, M. et al. A novel kinase, AATYK induces and promotes neuronal differentiation in a human neuroblastoma (SH-SY5Y) cell line. Brain Res. Mol. Brain Res. 77, 151–162 (2000).

pubmed: 10837911 doi: 10.1016/S0169-328X(00)00048-6

Mórotz, G. M. et al. A revised nomenclature for the lemur family of protein kinases. Commun. Biol. 7 (2024).

Ferrari, E., Naponelli, V. & Bettuzzi, S. Lemur tyrosine kinases and prostate cancer: a literature review. Int. J. Mol. Sci. 22 (2021).

Wendler, F., Purice, T.-M., Simon, T., Stebbing, J. & Giamas, G. The LMTK-family of kinases: emerging important players in cell physiology and pathogenesis. Biochim. Biophys. Acta Mol. Basis Dis. 1867 (2021).

Manning, G., Whyte, D. B., Martinez, R., Hunter, T. & Sudarsanam, S. The protein kinase complement of the human genome. Science 298, 1912–1934 (2002).

pubmed: 12471243 doi: 10.1126/science.1075762

Kawa, S. et al. Azoospermia in mice with targeted disruption of the Brek/Lmtk2 (brain-enriched kinase/lemur tyrosine kinase 2) gene. Proc. Natl Acad. Sci. USA 103, 19344–19349 (2006).

pubmed: 17158803 pmcid: 1748228 doi: 10.1073/pnas.0603603103

Komaki, K. et al. Lemur tail kinase 1 (LMTK1) regulates the endosomal localization of β-secretase BACE1. J. Biochem. 170, 729–738 (2021).

doi: 10.1093/jb/mvab094

Bencze, J. et al. Neuropathological characterization of Lemur tyrosine kinase 2 (LMTK2) in Alzheimer’s disease and neocortical Lewy body disease. Sci. Rep. 9 (2019).

Vella, V., Giamas, G. & Ditsiou, A. Diving into the dark kinome: lessons learned from LMTK3. Cancer Gene Ther. 29, 1077–1079 (2022).

pubmed: 34819628 doi: 10.1038/s41417-021-00408-3

Vezelis, A. et al. LMTK2 as potential biomarker for stratification between clinically insignificant and clinically significant prostate cancer. J. Oncol. 2021, 1–6 (2021).

doi: 10.1155/2021/8820366

Harries, L. W., Perry, J. R., McCullagh, P. & Crundwell, M. Alterations in LMTK2, MSMB and HNF1B gene expression are associated with the development of prostate cancer. BMC Cancer 10 (2010).

Jiang, T. et al. LMTK3 promotes tumorigenesis in bladder cancer via the ERK/MAPK pathway. FEBS Open Biol. 10, 2107–2121 (2020).

doi: 10.1002/2211-5463.12964

Stebbing, J. et al. LMTK3 confers chemo-resistance in breast cancer. Oncogene 37, 3113–3130 (2018).

pubmed: 29540829 pmcid: 5992129 doi: 10.1038/s41388-018-0197-0

Shi, H. et al. Lemur tyrosine kinase-3 is a significant prognostic marker for patients with colorectal cancer. Int. J. Clin. Exp. Pathol. 7, 1101–1107 (2014).

pubmed: 24695631 pmcid: 3971314

Ditsiou, A. et al. The multifaceted role of lemur tyrosine kinase 3 in health and disease. Open Biol. 11 (2021).

Zhou, C. et al. STYK1 promotes autophagy through enhancing the assembly of autophagy-specific class III phosphatidylinositol 3-kinase complex I. Autophagy 16, 1786–1806 (2020).

pubmed: 31696776 doi: 10.1080/15548627.2019.1687212

Liu, L. et al. A novel protein tyrosine kinase NOK that shares homology with platelet-derived growth factor/fibroblast growth factor receptors induces tumorigenesis and metastasis in nude mice. Cancer Res. 64, 3491–3499 (2004).

pubmed: 15150103 doi: 10.1158/0008-5472.CAN-03-2106

Trenker, R. & Jura, N. Receptor tyrosine kinase activation: from the ligand perspective. Curr. Opin. Cell Biol. 63, 174–185 (2020).

pubmed: 32114309 pmcid: 7813211 doi: 10.1016/j.ceb.2020.01.016

Lai, Y. et al. STYK1/NOK Promotes metastasis and epithelial-mesenchymal transition in non-small cell lung cancer by suppressing FoxO1 signaling. Front. Cell Dev. Biol. 9 (2021).

Kondoh, T., Kobayashi, D., Tsuji, N., Kuribayashi, K. & Watanabe, N. Overexpression of serine threonine tyrosine kinase 1/novel oncogene with kinase domain mRNA in patients with acute leukemia. Exp. Hematol. 37, 824–830 (2009).

pubmed: 19409952 doi: 10.1016/j.exphem.2009.04.010

Wang, Z. et al. STYK1 promotes epithelial-mesenchymal transition and tumor metastasis in human hepatocellular carcinoma through MEK/ERK and PI3K/AKT signaling. Sci Rep. 6, 1–12 (2016).

Jackson, K. A., Oprea, G., Handy, J. & Kimbro, K. S. Aberrant STYK1 expression in ovarian cancer tissues and cell lines. J. Ovar. Res. 2 (2009).

Ma, Z. et al. STYK1 promotes tumor growth and metastasis by reducing SPINT2/HAI-2 expression in non-small cell lung cancer. Cell Death Dis. 10 (2019).

Chung, S. et al. Overexpression of the potential kinase serine/threonine/tyrosine kinase 1 (STYK 1) in castration‐resistant prostate cancer. Cancer Sci. 100, 2109–2114 (2009).

pubmed: 19664042 pmcid: 11159893 doi: 10.1111/j.1349-7006.2009.01277.x

Zeng, S.-L. et al. STYK1/NOK affects cell cycle late mitosis and directly interacts with anaphase-promoting complex activator CDH1. Heliyon 8 (2022).

Chen, Y. et al. Point mutation at single tyrosine residue of novel oncogene NOK abrogates tumorigenesis in nude mice. Cancer Res. 65, 10838–10846 (2005).

pubmed: 16322230 doi: 10.1158/0008-5472.CAN-05-1091

Li, Y.-H. et al. The carboxyl terminal tyrosine 417 residue of NOK has an autoinhibitory effect on NOK-mediated signaling transductions. Biochem. Biophys. Res. Commun. 356, 444–449 (2007).

pubmed: 17367757 doi: 10.1016/j.bbrc.2007.02.154

Li, Y.-H. et al. Transmembrane helix of novel oncogene with kinase-domain (NOK) influences its oligomerization and limits the activation of RAS/MAPK signaling. Mol. Cells 27, 39–46 (2009).

pubmed: 19214432 doi: 10.1007/s10059-009-0003-5

Ding, X., Jiang, Q.-B., Li, R., Chen, S. & Zhang, S. NOK/STYK1 has a strong tendency towards forming aggregates and colocalises with epidermal growth factor receptor in endosomes. Biochem. Biophys. Res. Commun. 421, 468–473 (2012).

pubmed: 22516751 doi: 10.1016/j.bbrc.2012.04.016

Braicu, C. et al. A Comprehensive review on MAPK: a promising therapeutic target in cancer. Cancers(Basel) 11, 1–25 (2019).

Guo, X. & Wang, X.-F. Signaling cross-talk between TGF-β/BMP and other pathways. Cell Res. 19, 71–88 (2009).

pubmed: 19002158 doi: 10.1038/cr.2008.302

Mahajan, K. & Mahajan, N. P. Cross-talk of tyrosine kinases with the DNA damage signaling pathways. Nucleic Acids Res. 43, 10588–10601 (2015).

pubmed: 26546517 pmcid: 4678820 doi: 10.1093/nar/gkv1166

Regad, T. Targeting RTK signaling pathways in cancer. Cancers 7, 1758–1784 (2015).

pubmed: 26404379 pmcid: 4586793 doi: 10.3390/cancers7030860

Sudhesh Dev, S., Zainal Abidin, S. A., Farghadani, R., Othman, I. & Naidu, R. Receptor tyrosine kinases and their signaling pathways as therapeutic targets of curcumin in cancer. Front. Pharmacol. 12, 1–26 (2021).

Schlessinger, J. Cell signaling by receptor tyrosine kinases. Cell 103, 211–225 (2000).

pubmed: 11057895 doi: 10.1016/S0092-8674(00)00114-8

Lo, H.-W. & Hung, M.-C. Nuclear EGFR signalling network in cancers: linking EGFR pathway to cell cycle progression, nitric oxide pathway and patient survival. Br. J. Cancer 94, 184–188 (2006).

pubmed: 16434982 pmcid: 2361115 doi: 10.1038/sj.bjc.6602941

Haeusler, R. A., McGraw, T. E. & Accili, D. Biochemical and cellular properties of insulin receptor signalling. Nat. Rev. Mol. Cell Biol. 19, 31–44 (2018).

pubmed: 28974775 doi: 10.1038/nrm.2017.89

Andrae, J., Gallini, R. & Betsholtz, C. Role of platelet-derived growth factors in physiology and medicine. Genes Dev. 22, 1276–1312 (2008).

pubmed: 18483217 pmcid: 2732412 doi: 10.1101/gad.1653708

Mineur, P. et al. Newly identified biologically active and proteolysis-resistant VEGF-A isoform VEGF111 is induced by genotoxic agents. J. Cell Biol. 179, 1261–1273 (2007).

pubmed: 18086921 pmcid: 2140032 doi: 10.1083/jcb.200703052

Toledo, R. A. et al. Exome sequencing of plasma DNA portrays the mutation landscape of colorectal cancer and discovers mutated VEGFR2 receptors as modulators of antiangiogenic therapies. Clin. Cancer Res 24, 3550–3559 (2018).

pubmed: 29588308 doi: 10.1158/1078-0432.CCR-18-0103

Azoury, S. C., Reddy, S., Shukla, V. & Deng, C.-X. Fibroblast growth factor receptor 2 (FGFR2) mutation related syndromic craniosynostosis. Int. J. Biol. Sci. 13, 1479–1488 (2017).

pubmed: 29230096 pmcid: 5723914 doi: 10.7150/ijbs.22373

Williams, J. A. et al. Cholecystokinin activates a variety of intracellular signal transduction mechanisms in rodent pancreatic acinar cells. Pharm. Toxicol. 91, 297–303 (2002).

doi: 10.1034/j.1600-0773.2002.910606.x

Vidal, A. & Redmer, T. Decoding the role of CD271 in melanoma. Cancers 12 (2020).

Lam, B. Q., Dai, L. & Qin, Z. The role of HGF/c-MET signaling pathway in lymphoma. J. Hematol. Oncol. 9, 1–8 (2016).

Gucciardo, E., Sugiyama, N. & Lehti, K. Eph- and ephrin-dependent mechanisms in tumor and stem cell dynamics. Cell Mol. Life Sci. 71, 3685–3710 (2014).

pubmed: 24794629 pmcid: 11113620 doi: 10.1007/s00018-014-1633-0

Pasquale, E. B. Eph receptors and ephrins in cancer: bidirectional signalling and beyond. Nat. Rev. Cancer 10, 165–180 (2010).

pubmed: 20179713 pmcid: 2921274 doi: 10.1038/nrc2806

Saharinen, P., Eklund, L. & Alitalo, K. Therapeutic targeting of the angiopoietin–TIE pathway. Nat. Rev. Drug Discov. 16, 635–661 (2017).

pubmed: 28529319 doi: 10.1038/nrd.2016.278

Zhang, X. et al. Potential of tyrosine kinase receptor TIE-1 as novel therapeutic target in high-PI3K-expressing ovarian cancer. Cancers 12 (2020).

Rodriguez-Trillo, A. et al. Non-canonical WNT5A signaling through RYK contributes to aggressive phenotype of the rheumatoid fibroblast-like synoviocytes. Front. Immunol. 11, 1–13 (2020).

doi: 10.3389/fimmu.2020.555245

Mariadoss, A. V. A. & Wang, C.-Z. Exploring the cellular and molecular mechanism of discoidin domain receptors (DDR1 and DDR2) in bone formation, regeneration, and its associated disease conditions. Int. J. Mol. Sci. 24 (2023).

Goto, K., Kawahara, I., Kuniyasu, H. & Takaki, M. A protein tyrosine kinase receptor, c-RET signaling pathway contributes to the enteric neurogenesis induced by a 5-HT4 receptor agonist at an anastomosis after transection of the gut in rodents. J. Physiol. Sci. 65, 377–383 (2015).

pubmed: 25850922 pmcid: 10717718 doi: 10.1007/s12576-015-0377-4

Regua, A. T., Najjar, M. & Lo, H.-W. RET signaling pathway and RET inhibitors in human cancer. Front. Oncol. 12 (2022).

Hasan, M. K., Ghia, E. M., Rassenti, L. Z., Widhopf, G. F. & Kipps, T. J. Wnt5a enhances proliferation of chronic lymphocytic leukemia and ERK1/2 phosphorylation via a ROR1/DOCK2-dependent mechanism. Leukemia 35, 1621–1630 (2021).

pubmed: 33097837 doi: 10.1038/s41375-020-01055-7

Chen, Y. et al. Cirmtuzumab blocks Wnt5a/ROR1 stimulation of NF-κB to repress autocrine STAT3 activation in chronic lymphocytic leukemia. Blood 134, 1084–1094 (2019).

pubmed: 31409670 pmcid: 6764264 doi: 10.1182/blood.2019001366

Villarroel, A. et al. Src and Fyn define a new signaling cascade activated by canonical and non-canonical Wnt ligands and required for gene transcription and cell invasion. Cell Mol. Life Sci. 77, 919–935 (2020).

pubmed: 31312879 doi: 10.1007/s00018-019-03221-2

Endo, M., Kamizaki, K. & Minami, Y. The Ror-family receptors in development, tissue regeneration and age-related disease. Front. Cell. Dev. Biol. 10, (2022).

Della Corte, C. M. et al. Role and targeting of anaplastic lymphoma kinase in cancer. Mol. Cancer 17 (2018).

Shiota, M. et al. Hyperphosphorylation of a novel 80 kDa protein-tyrosine kinase similar to Ltk in a human Ki-1 lymphoma cell line, AMS3. Oncogene 9, 1567–1574 (1994).

pubmed: 8183550

Fruman, D. A. et al. The PI3K pathway in human disease. Cell 170, 605–635 (2017).

pubmed: 28802037 pmcid: 5726441 doi: 10.1016/j.cell.2017.07.029

Yu, H., Pardoll, D. & Jove, R. STATs in cancer inflammation and immunity: a leading role for STAT3. Nat. Rev. Cancer 9, 798–809 (2009).

pubmed: 19851315 pmcid: 4856025 doi: 10.1038/nrc2734

Chang, F. et al. Signal transduction mediated by the Ras/Raf/MEK/ERK pathway from cytokine receptors to transcription factors: potential targeting for therapeutic intervention. Leukemia 17, 1263–1293 (2003).

pubmed: 12835716 doi: 10.1038/sj.leu.2402945

Zhang, Z., Zhou, X., Shen, H., Wang, D. & Wang, Y. Phosphorylated ERK is a potential predictor of sensitivity to sorafenib when treating hepatocellular carcinoma: evidence from an in vitro study. BMC Med. 7 (2009).

McCubrey, J. A. et al. Roles of the Raf/MEK/ERK pathway in cell growth, malignant transformation and drug resistance. Biochim. Biophys. Acta 1773, 1263–1284 (2007).

pubmed: 17126425 doi: 10.1016/j.bbamcr.2006.10.001

Steelman, L. S. et al. JAK/STAT, Raf/MEK/ERK, PI3K/Akt and BCR-ABL in cell cycle progression and leukemogenesis. Leukemia 18, 189–218 (2004).

pubmed: 14737178 doi: 10.1038/sj.leu.2403241

Stirewalt, D. L. et al. FLT3, RAS, and TP53 mutations in elderly patients with acute myeloid leukemia. Blood 97, 3589–3595 (2001).

pubmed: 11369655 doi: 10.1182/blood.V97.11.3589

Yan, J., Roy, S., Apolloni, A., Lane, A. & Hancock, J. F. Ras isoforms vary in their ability to activate Raf-1 and phosphoinositide 3-kinase. J. Biol. Chem. 273, 24052–24056 (1998).

pubmed: 9727023 doi: 10.1074/jbc.273.37.24052

Garnett, M. J. & Marais, R. Guilty as charged: B-RAF is a human oncogene. Cancer Cell 6, 313–319 (2004).

pubmed: 15488754 doi: 10.1016/j.ccr.2004.09.022

Shelton, J. G. et al. B-raf and insulin synergistically prevent apoptosis and induce cell cycle progression in hematopoietic cells. Cell Cycle 3, 189–196 (2004).

pubmed: 14712088

Blalock, W. L. et al. A conditionally-active form of MEK1 results in autocrine tranformation of human and mouse hematopoietic cells. Oncogene 19, 526–536 (2000).

pubmed: 10698522 doi: 10.1038/sj.onc.1203337

Nakano, H. et al. Differential regulation of IkappaB kinase alpha and beta by two upstream kinases, NF-kappaB-inducing kinase and mitogen-activated protein kinase/ERK kinase kinase-1. Proc. Natl Acad. Sci. USA 95, 3537–3542 (1998).

pubmed: 9520401 pmcid: 19871 doi: 10.1073/pnas.95.7.3537

Nandan, M. O. & Yang, V. W. Genetic and chemical models of colorectal cancer in mice. Curr. Colorectal Cancer Rep. 6, 51–59 (2010).

pubmed: 20376303 pmcid: 2850068 doi: 10.1007/s11888-010-0046-1

Reuter, C. W., Morgan, M. A. & Bergmann, L. Targeting the Ras signaling pathway: a rational, mechanism-based treatment for hematologic malignancies? Blood 96, 1655–1669 (2000).

pubmed: 10961860 doi: 10.1182/blood.V96.5.1655

Vaughn, C. P., Zobell, S. D., Furtado, L. V., Baker, C. L. & Samowitz, W. S. Frequency of KRAS, BRAF, and NRAS mutations in colorectal cancer. Genes Chromosomes Cancer 50, 307–312 (2011).

pubmed: 21305640 doi: 10.1002/gcc.20854

Almoguera, C. et al. Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell 53, 549–554 (1988).

pubmed: 2453289 doi: 10.1016/0092-8674(88)90571-5

Bizebard, T. et al. Crystallization and preliminary X-ray diffraction studies of a monoclonal antibody Fab fragment specific for an influenza virus haemagglutinin and of an escape mutant of that haemagglutinin. J. Mol. Biol. 216, 513–514 (1990).

pubmed: 2258927 doi: 10.1016/0022-2836(90)90378-Y

Rajasekharan, S. & Raman, T. Ras and Ras mutations in cancer. Open Life Sci. 8, 609–624 (2013).

doi: 10.2478/s11535-013-0158-5

Bazan, V. et al. Specific codon 13 K-ras mutations are predictive of clinical outcome in colorectal cancer patients, whereas codon 12 K-ras mutations are associated with mucinous histotype. Ann. Oncol. 13, 1438–1446 (2002).

pubmed: 12196370 doi: 10.1093/annonc/mdf226

Parsons, B. L., Culp, S. J., Manjanatha, M. G. & Heflich, R. H. Occurrence of H-ras codon 61 CAA to AAA mutation during mouse liver tumor progression. Carcinogenesis 23, 943–948 (2002).

pubmed: 12082015 doi: 10.1093/carcin/23.6.943

Bos, J. L. ras oncogenes in human cancer: a review. Cancer Res. 49, 4682–4689 (1989).

pubmed: 2547513

Edkins, S. et al. Recurrent KRAS codon 146 mutations in human colorectal cancer. Cancer Biol. Ther. 5, 928–932 (2006).

pubmed: 16969076 doi: 10.4161/cbt.5.8.3251

Imamura, Y. et al. Specific mutations in KRAS codons 12 and 13, and patient prognosis in 1075 BRAF wild-type colorectal cancers. Clin. Cancer Res. 18, 4753–4763 (2012).

pubmed: 22753589 pmcid: 3624899 doi: 10.1158/1078-0432.CCR-11-3210

Quilliam, L. A. et al. M-Ras/R-Ras3, a transforming ras protein regulated by Sos1, GRF1, and p120 Ras GTPase-activating protein, interacts with the putative Ras effector AF6. J. Biol. Chem. 274, 23850–23857 (1999).

pubmed: 10446149 doi: 10.1074/jbc.274.34.23850

Irahara, N. et al. NRAS mutations are rare in colorectal cancer. Diagn. Mol. Pathol. 19, 157–163 (2010).

pubmed: 20736745 pmcid: 2929976 doi: 10.1097/PDM.0b013e3181c93fd1

Omholt, K. et al. Screening of N-ras codon 61 mutations in paired primary and metastatic cutaneous melanomas: mutations occur early and persist throughout tumor progression. Clin. Cancer Res. 8, 3468–3474 (2002).

pubmed: 12429636

Cascetta, P. et al. KRAS in NSCLC: state of the art and future perspectives. Cancers 14 (2022).

Veluswamy, R., Mack, P. C., Houldsworth, J., Elkhouly, E. & Hirsch, F. R. KRAS G12C-mutant non-small cell lung cancer. J. Mol. Diagn. 23, 507–520 (2021).

pubmed: 33618059 doi: 10.1016/j.jmoldx.2021.02.002

Qunaj, L., May, M. S., Neugut, A. I. & Herzberg, B. O. Prognostic and therapeutic impact of the KRAS G12C mutation in colorectal cancer. Front Oncol 13 (2023).

Chen, K., Zhang, Y., Qian, L. & Wang, P. Emerging strategies to target RAS signaling in human cancer therapy. J. Hematol. Oncol. 14 (2021).

Hunter, J. C. et al. In situ selectivity profiling and crystal structure of SML-8-73-1, an active site inhibitor of oncogenic K-Ras G12C. Proc. Natl Acad. Sci. USA 111, 8895–8900 (2014).

pubmed: 24889603 pmcid: 4066474 doi: 10.1073/pnas.1404639111

Hallin, J. et al. The KRASG12C inhibitor MRTX849 provides insight toward therapeutic susceptibility of KRAS-mutant cancers in mouse models and patients. Cancer Discov. 10, 54–71 (2020).

pubmed: 31658955 doi: 10.1158/2159-8290.CD-19-1167

Canon, J. et al. The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity. Nature 575, 217–223 (2019).

pubmed: 31666701 doi: 10.1038/s41586-019-1694-1

Nandan, M. O. & Yang, V. W. An update on the biology of RAS/RAF mutations in colorectal cancer. Curr. Colorectal Cancer Rep. 7, 113–120 (2011).

pubmed: 21625338 pmcid: 3103074 doi: 10.1007/s11888-011-0086-1

Marais, R., Light, Y., Paterson, H. F., Mason, C. S. & Marshall, C. J. Differential regulation of Raf-1, A-Raf, and B-Raf by oncogenic ras and tyrosine kinases. J. Biol. Chem. 272, 4378–4383 (1997).

pubmed: 9020159 doi: 10.1074/jbc.272.7.4378

Dobre, E.-G., Nichita, L., Popp, C., Zurac, S. & Neagu, M. Assessment of RAS-RAF-MAPK pathway mutation status in healthy skin, benign nevi, and cutaneous melanomas: pilot study using droplet digital PCR. Int. J. Mol. Sci. 25 (2024).

Mayr, D., Hirschmann, A., Löhrs, U. & Diebold, J. KRAS and BRAF mutations in ovarian tumors: a comprehensive study of invasive carcinomas, borderline tumors and extraovarian implants. Gynecol. Oncol. 103, 883–887 (2006).

pubmed: 16806438 doi: 10.1016/j.ygyno.2006.05.029

Jiang, L., Chu, H. & Zheng, H. B-Raf mutation and papillary thyroid carcinoma patients. Oncol. Lett. 11, 2699–2705 (2016).

pubmed: 27073540 pmcid: 4812206 doi: 10.3892/ol.2016.4298

Clarke, C. N. & Kopetz, E. S. BRAF mutant colorectal cancer as a distinct subset of colorectal cancer: clinical characteristics, clinical behavior, and response to targeted therapies. J. Gastrointest. Oncol. 6, 660–667 (2015).

pubmed: 26697199 pmcid: 4671844

Rajagopalan, H. et al. Tumorigenesis: RAF/RAS oncogenes and mismatch-repair status. Nature 418 (2002).

Davies, H. et al. Mutations of the BRAF gene in human cancer. Nature 417, 949–954 (2002).

pubmed: 12068308 doi: 10.1038/nature00766

Garnett, M. J., Rana, S., Paterson, H., Barford, D. & Marais, R. Wild-type and mutant B-RAF activate C-RAF through distinct mechanisms involving heterodimerization. Mol. Cell 20, 963–969 (2005).

pubmed: 16364920 doi: 10.1016/j.molcel.2005.10.022

Śmiech, M., Leszczyński, P., Kono, H., Wardell, C. & Taniguchi, H. Emerging BRAF mutations in cancer progression and their possible effects on transcriptional networks. Genes 11 (2020).

Walker, B. A. et al. Identification of novel mutational drivers reveals oncogene dependencies in multiple myeloma. Blood 132, 587–597 (2018).

pubmed: 29884741 pmcid: 6097138 doi: 10.1182/blood-2018-03-840132

Boyle, E. M. et al. BRAF and DIS3 mutations associate with adverse outcome in a long-term follow-up of patients with multiple myeloma. Clin. Cancer Res. 26, 2422–2432 (2020).

pubmed: 31988198 doi: 10.1158/1078-0432.CCR-19-1507

Wu, X. et al. Mutations in BRAF codons 594 and 596 predict good prognosis in melanoma. Oncol. Lett. 14, 3601–3605 (2017).

pubmed: 28927118 pmcid: 5587919 doi: 10.3892/ol.2017.6608

Cremolini, C. et al. BRAF codons 594 and 596 mutations identify a new molecular subtype of metastatic colorectal cancer at favorable prognosis. Ann. Oncol. 26, 2092–2097 (2015).

pubmed: 26153495 doi: 10.1093/annonc/mdv290

Zheng, G. et al. Clinical detection and categorization of uncommon and concomitant mutations involving BRAF. BMC Cancer 15 (2015).

Heidorn, S. J. et al. Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor progression through CRAF. Cell 140, 209–221 (2010).

pubmed: 20141835 pmcid: 2872605 doi: 10.1016/j.cell.2009.12.040

Schirripa, M. et al. Class 1, 2, and 3 BRAF-mutated metastatic colorectal cancer: a detailed clinical, pathologic, and molecular characterization. Clin. Cancer Res. 25, 3954–3961 (2019).

pubmed: 30967421 doi: 10.1158/1078-0432.CCR-19-0311

Park, E. et al. Architecture of autoinhibited and active BRAF-MEK1-14-3-3 complexes. Nature 575, 545–550 (2019).

pubmed: 31581174 pmcid: 7014971 doi: 10.1038/s41586-019-1660-y

Haling, J. R. et al. Structure of the BRAF-MEK complex reveals a kinase activity independent role for BRAF in MAPK signaling. Cancer Cell 26, 402–413 (2014).

pubmed: 25155755 doi: 10.1016/j.ccr.2014.07.007

Wan, P. T. C. et al. Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF. Cell 116, 855–867 (2004).

pubmed: 15035987 doi: 10.1016/S0092-8674(04)00215-6

Noeparast, A. et al. CRAF mutations in lung cancer can be oncogenic and predict sensitivity to combined type II RAF and MEK inhibition. Oncogene 38, 5933–5941 (2019).

pubmed: 31285551 pmcid: 6756226 doi: 10.1038/s41388-019-0866-7

Isnaldi, E. et al. Clinico-pathological associations and concomitant mutations of the RAS/RAF pathway in metastatic colorectal cancer. J. Transl. Med. 17 (2019).

Marino, K. A., Sutto, L. & Gervasio, F. L. The effect of a widespread cancer-causing mutation on the inactive to active dynamics of the B-Raf kinase. J. Am. Chem. Soc. 137, 5280–5283 (2015).

pubmed: 25868080 doi: 10.1021/jacs.5b01421

Salzmann, M. et al. MEK inhibitors for pre-treated, NRAS-mutated metastatic melanoma: a multi-centre, retrospective study. Eur. J. Cancer 166, 24–32 (2022).

pubmed: 35272084 doi: 10.1016/j.ejca.2022.02.008

Marani, A., Gioacchini, H., Paolinelli, M., Offidani, A. & Campanati, A. Potential drug-drug interactions with mitogen-activated protein kinase (MEK) inhibitors used to treat melanoma. Expert Opin. Drug Metab. Toxicol. 19, 555–567 (2023).

pubmed: 37659065 doi: 10.1080/17425255.2023.2255519

Akinleye, A., Furqan, M., Mukhi, N., Ravella, P. & Liu, D. MEK and the inhibitors: from bench to bedside. J. Hematol. Oncol. 6 (2013).

Gao, Y. et al. V211D mutation in MEK1 causes resistance to MEK inhibitors in colon cancer. Cancer Discov. 9, 1182–1191 (2019).

pubmed: 31227518 pmcid: 6726556 doi: 10.1158/2159-8290.CD-19-0356

Gao, Y. et al. Allele-specific mechanisms of activation of MEK1 mutants determine their properties. Cancer Discov. 8, 648–661 (2018).

pubmed: 29483135 pmcid: 6112572 doi: 10.1158/2159-8290.CD-17-1452

Kubota, Y. et al. Qualitative differences in disease-associated MEK mutants reveal molecular signatures and aberrant signaling-crosstalk in cancer. Nat. Commun. 13 (2022).

Emery, C. M. et al. MEK1 mutations confer resistance to MEK and B-RAF inhibition. Proc. Natl Acad. Sci. USA 106, 20411–20416 (2009).

pubmed: 19915144 pmcid: 2777185 doi: 10.1073/pnas.0905833106

Sang, D. et al. Ancestral reconstruction reveals mechanisms of ERK regulatory evolution. Elife 8 (2019).

Martin-Vega, A. & Cobb, M. H. Navigating the ERK1/2 MAPK Cascade. Biomolecules 13 (2023).

Balmanno, K. et al. ERK1/2 inhibitors act as monovalent degraders inducing ubiquitylation and proteasome-dependent turnover of ERK2, but not ERK1. Biochem. J. 480, 587–605 (2023).

pubmed: 37018014 doi: 10.1042/BCJ20220598

Wortzel, I. & Seger, R. The ERK cascade: distinct functions within various subcellular organelles. Genes Cancer 2, 195–209 (2011).

pubmed: 21779493 pmcid: 3128630 doi: 10.1177/1947601911407328

Smorodinsky-Atias, K., Soudah, N. & Engelberg, D. Mutations that confer drug-resistance, oncogenicity and intrinsic activity on the ERK MAP kinases-current state of the art. Cells 9 (2020).

Lawrence, M. S. et al. Discovery and saturation analysis of cancer genes across 21 tumour types. Nature 505, 495–501 (2014).

pubmed: 24390350 pmcid: 4048962 doi: 10.1038/nature12912

Ojesina, A. I. et al. Landscape of genomic alterations in cervical carcinomas. Nature 506, 371–375 (2014).

pubmed: 24390348 doi: 10.1038/nature12881

Goetz, E. M., Ghandi, M., Treacy, D. J., Wagle, N. & Garraway, L. A. ERK mutations confer resistance to mitogen-activated protein kinase pathway inhibitors. Cancer Res. 74, 7079–7089 (2014).

pubmed: 25320010 pmcid: 4300142 doi: 10.1158/0008-5472.CAN-14-2073

Yu, L., Wei, J. & Liu, P. Attacking the PI3K/Akt/mTOR signaling pathway for targeted therapeutic treatment in human cancer. Semin Cancer Biol. 85, 69–94 (2022).

pubmed: 34175443 doi: 10.1016/j.semcancer.2021.06.019

Vivanco, I. & Sawyers, C. L. The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat. Rev. Cancer 2, 489–501 (2002).

pubmed: 12094235 doi: 10.1038/nrc839

Mohan, C. D. et al. Trisubstituted-imidazoles induce apoptosis in human breast cancer cells by targeting the oncogenic PI3K/Akt/mTOR signaling pathway. PLoS One 11 (2016).

Janku, F., Yap, T. A. & Meric-Bernstam, F. Targeting the PI3K pathway in cancer: are we making headway? Nat. Rev. Clin. Oncol. 15, 273–291 (2018).

pubmed: 29508857 doi: 10.1038/nrclinonc.2018.28

Manning, B. D. & Cantley, L. C. AKT/PKB signaling: navigating downstream. Cell 129, 1261–1274 (2007).

pubmed: 17604717 pmcid: 2756685 doi: 10.1016/j.cell.2007.06.009

Glaviano, A. et al. PI3K/AKT/mTOR signaling transduction pathway and targeted therapies in cancer. Mol Cancer 22 (2023).

Juric, D. et al. Convergent loss of PTEN leads to clinical resistance to a PI(3)Kα inhibitor. Nature 518, 240–244 (2015).

pubmed: 25409150 doi: 10.1038/nature13948

Razavi, P. et al. Alterations in PTEN and ESR1 promote clinical resistance to alpelisib plus aromatase inhibitors. Nat. Cancer 1, 382–393 (2020).

pubmed: 32864625 pmcid: 7450824 doi: 10.1038/s43018-020-0047-1

Masson, G. R. & Williams, R. L. Structural mechanisms of PTEN regulation. Cold Spring Harb. Perspect. Med. 10, 1–13 (2020).

Steck, P. A. et al. Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nat. Genet. 15, 356–362 (1997).

pubmed: 9090379 doi: 10.1038/ng0497-356

Lee, Y.-R., Chen, M. & Pandolfi, P. P. The functions and regulation of the PTEN tumour suppressor: new modes and prospects. Nat. Rev. Mol. Cell Biol. 19, 547–562 (2018).

pubmed: 29858604 doi: 10.1038/s41580-018-0015-0

Papa, A. & Pandolfi, P. P. The PTEN

Yang, Z.-Z. et al. Physiological functions of protein kinase B/Akt. Biochem Soc. Trans. 32, 350–354 (2004).

pubmed: 15046607 doi: 10.1042/bst0320350

Garofalo, R. S. et al. Severe diabetes, age-dependent loss of adipose tissue, and mild growth deficiency in mice lacking Akt2/PKB beta. J. Clin. Investig. 112, 197–208 (2003).

pubmed: 12843127 pmcid: 164287 doi: 10.1172/JCI16885

Chen, W. S. et al. Growth retardation and increased apoptosis in mice with homozygous disruption of the Akt1 gene. Genes Dev. 15, 2203–2208 (2001).

pubmed: 11544177 pmcid: 312770 doi: 10.1101/gad.913901

Xie, J. & Weiskirchen, R. What does the “AKT” stand for in the name “AKT Kinase”? some historical comments. Front. Oncol. 10 (2020).

Bao, F. et al. Akt scaffold proteins: the key to controlling specificity of Akt signaling. Am. J. Physiol. Cell Physiol. 321, 429–442 (2021).

doi: 10.1152/ajpcell.00146.2020

Carpten, J. D. et al. A transforming mutation in the pleckstrin homology domain of AKT1 in cancer. Nature 448, 439–444 (2007).

pubmed: 17611497 doi: 10.1038/nature05933

Lauring, J. et al. Knock in of the AKT1 E17K mutation in human breast epithelial cells does not recapitulate oncogenic PIK3CA mutations. Oncogene 29, 2337–2345 (2010).

pubmed: 20101210 pmcid: 3042798 doi: 10.1038/onc.2009.516

Davies, B. R. et al. Tumors with AKT1E17K mutations are rational targets for single agent or combination therapy with akt inhibitors. Mol. Cancer Ther. 14, 2441–2451 (2015).

pubmed: 26351323 doi: 10.1158/1535-7163.MCT-15-0230

Rudolph, M. et al. AKT1 (E17K) mutation profiling in breast cancer: prevalence, concurrent oncogenic alterations, and blood-based detection. BMC Cancer 16 (2016).

Alves, C. P. et al. AKT1low quiescent cancer cells promote solid tumor growth. Mol. Cancer Ther. 17, 254–263 (2018).

pubmed: 29054988 doi: 10.1158/1535-7163.MCT-16-0868

Guo, G. et al. Oncogenic E17K mutation in the pleckstrin homology domain of AKT1 promotes v-Abl-mediated pre-B-cell transformation and survival of Pim-deficient cells. Oncogene 29, 3845–3853 (2010).

pubmed: 20440266 doi: 10.1038/onc.2010.149

Chen, Y. et al. Effect of AKT1 (p. E17K) hotspot mutation on malignant tumorigenesis and prognosis. Front. Cell Dev. Biol. 8 (2020).

Hyman, D. M. et al. AKT inhibition in solid tumors With AKT1 mutations. J. Clin. Oncol. 35, 2251–2259 (2017).

pubmed: 28489509 pmcid: 5501365 doi: 10.1200/JCO.2017.73.0143

Shrestha Bhattarai, T. et al. AKT mutant allele-specific activation dictates pharmacologic sensitivities. Nat. Commun. 13, 1–11 (2022).

doi: 10.1038/s41467-022-29638-1

Shi, H. et al. A novel AKT1 mutant amplifies an adaptive melanoma response to BRAF inhibition. Cancer Discov. 4, 69–79 (2014).

pubmed: 24265152 doi: 10.1158/2159-8290.CD-13-0279

Saxton, R. A. & Sabatini, D. M. mTOR signaling in growth, metabolism, and disease. Cell 168, 960–976 (2017).

pubmed: 28283069 pmcid: 5394987 doi: 10.1016/j.cell.2017.02.004

Zou, Z., Tao, T., Li, H. & Zhu, X. mTOR signaling pathway and mTOR inhibitors in cancer: progress and challenges. Cell Biosci. 10, 1–11 (2020).

Panwar, V. et al. Multifaceted role of mTOR (mammalian target of rapamycin) signaling pathway in human health and disease. Signal Transduct. Target. Ther. 8 (2023).

Grabiner, B. C. et al. A diverse array of cancer-associated MTOR mutations are hyperactivating and can predict rapamycin sensitivity. Cancer Discov. 4, 554–563 (2014).

pubmed: 24631838 pmcid: 4012430 doi: 10.1158/2159-8290.CD-13-0929

Yamaguchi, H. et al. Transforming somatic mutations of mammalian target of rapamycin kinase in human cancer. Cancer Sci. 106, 1687–1692 (2015).

pubmed: 26432419 pmcid: 4714661 doi: 10.1111/cas.12828

Murugan, A. K., Liu, R. & Xing, M. Identification and characterization of two novel oncogenic mTOR mutations. Oncogene 38, 5211–5226 (2019).

pubmed: 30918329 pmcid: 6597304 doi: 10.1038/s41388-019-0787-5

Rodríguez-Moreno, J. F. et al. Exceptional response to temsirolimus in a metastatic clear cell renal cell carcinoma with an early novel MTOR-activating mutation. J. Natl Compr. Cancer Netw. 15, 1310–1315 (2017).

doi: 10.6004/jnccn.2017.7018

Ghosh, A. P. et al. Point mutations of the mTOR-RHEB pathway in renal cell carcinoma. Oncotarget 6, 17895–17910 (2015).

pubmed: 26255626 pmcid: 4627224 doi: 10.18632/oncotarget.4963

Kong, Y. et al. Analysis of mTOR gene aberrations in melanoma patients and evaluation of their sensitivity to PI3K–AKT–mTOR pathway inhibitors. Clin. Cancer Res. 22, 1018–1027 (2016).

pubmed: 26490311 doi: 10.1158/1078-0432.CCR-15-1110

Wu, T.-J. et al. Identification of a non-gatekeeper hot spot for drug-resistant mutations in mTOR kinase. Cell Rep. 11, 446–459 (2015).

pubmed: 25865887 pmcid: 4761412 doi: 10.1016/j.celrep.2015.03.040

Wagle, N. et al. Response and acquired resistance to everolimus in anaplastic thyroid cancer. N. Engl. J. Med. 371, 1426–1433 (2014).

pubmed: 25295501 pmcid: 4564868 doi: 10.1056/NEJMoa1403352

Owen, K. L., Brockwell, N. K. & Parker, B. S. JAK-STAT signaling: a double-edged sword of immune regulation and cancer progression. Cancers 11 (2019).

Nan, J., Wang, Y., Yang, J. & Stark, G. R. IRF9 and unphosphorylated STAT2 cooperate with NF-κB to drive IL6 expression. Proc. Natl Acad. Sci. USA 115, 3906–3911 (2018).

pubmed: 29581268 pmcid: 5899435 doi: 10.1073/pnas.1714102115

Cheon, H. & Stark, G. R. Unphosphorylated STAT1 prolongs the expression of interferon-induced immune regulatory genes. Proc. Natl Acad. Sci. USA 106, 9373–9378 (2009).

pubmed: 19478064 pmcid: 2688000 doi: 10.1073/pnas.0903487106

Ivashkiv, L. B. & Donlin, L. T. Regulation of type I interferon responses. Nat. Rev. Immunol. 14, 36–49 (2014).

pubmed: 24362405 pmcid: 4084561 doi: 10.1038/nri3581

Platanias, L. C. Mechanisms of type-I- and type-II-interferon-mediated signalling. Nat. Rev. Immunol. 5, 375–386 (2005).

pubmed: 15864272 doi: 10.1038/nri1604

Fuertes, M. B., Woo, S.-R., Burnett, B., Fu, Y.-X. & Gajewski, T. F. Type I interferon response and innate immune sensing of cancer. Trends Immunol. 34, 67–73 (2013).

pubmed: 23122052 doi: 10.1016/j.it.2012.10.004

Battistini, A. Interferon regulatory factors in hematopoietic cell differentiation and immune regulation. J. Interferon Cytokine Res. 29, 765–780 (2009).

pubmed: 19929577 doi: 10.1089/jir.2009.0030

Ragimbeau, J. et al. The tyrosine kinase Tyk2 controls IFNAR1 cell surface expression. EMBO J. 22, 537–547 (2003).

pubmed: 12554654 pmcid: 140723 doi: 10.1093/emboj/cdg038

Hofmann, S. R. et al. Jak3-independent trafficking of the common gamma chain receptor subunit: chaperone function of Jaks revisited. Mol. Cell Biol. 24, 5039–5049 (2004).

pubmed: 15143194 pmcid: 416416 doi: 10.1128/MCB.24.11.5039-5049.2004

Tortolani, P. J. et al. Regulation of JAK3 expression and activation in human B cells and B cell malignancies. J. Immunol. 155, 5220–5226 (1995).

pubmed: 7594533 doi: 10.4049/jimmunol.155.11.5220

Musso, T. et al. Regulation of JAK3 expression in human monocytes: phosphorylation in response to interleukins 2, 4, and 7. J. Exp. Med. 181, 1425–1431 (1995).

pubmed: 7535338 doi: 10.1084/jem.181.4.1425

Kawamura, M. et al. Molecular cloning of L-JAK, a Janus family protein-tyrosine kinase expressed in natural killer cells and activated leukocytes. Proc. Natl Acad. Sci. USA 91, 6374–6378 (1994).

pubmed: 8022790 pmcid: 44204 doi: 10.1073/pnas.91.14.6374

Karaghiosoff, M. et al. Central role for type I interferons and Tyk2 in lipopolysaccharide-induced endotoxin shock. Nat. Immunol. 4, 471–477 (2003).

pubmed: 12679810 doi: 10.1038/ni910

Yamaoka, K. et al. The Janus kinases (Jaks). Genome Biol. 5, 1–6 (2004).

Copeland, N. G. et al. Distribution of the mammalian Stat gene family in mouse chromosomes. Genomics 29, 225–228 (1995).

pubmed: 8530075 doi: 10.1006/geno.1995.1235

Heim, M. H. The STAT protein family. in Signal Transducers and Activators of Transcription (STATs) 11–26 (Springer Netherlands, Dordrecht, 2003). https://doi.org/10.1007/978-94-017-3000-6_2 .

O’Shea, J. J. & Murray, P. J. Cytokine signaling modules in inflammatory responses. Immunity 28, 477–487 (2008).

pubmed: 18400190 pmcid: 2782488 doi: 10.1016/j.immuni.2008.03.002

Schindler, C., Levy, D. E. & Decker, T. JAK-STAT signaling: from interferons to cytokines. J. Biol. Chem. 282, 20059–20063 (2007).

pubmed: 17502367 doi: 10.1074/jbc.R700016200

Zhou, L., Chong, M. M. W. & Littman, D. R. Plasticity of CD4+ T cell lineage differentiation. Immunity 30, 646–655 (2009).

pubmed: 19464987 doi: 10.1016/j.immuni.2009.05.001

Wang, H., Lafdil, F., Kong, X. & Gao, B. Signal transducer and activator of transcription 3 in liver diseases: a novel therapeutic target. Int. J. Biol. Sci. 7, 536–550 (2011).

pubmed: 21552420 pmcid: 3088876 doi: 10.7150/ijbs.7.536

Bar-Natan, M., Nelson, E. A., Xiang, M. & Frank, D. A. STAT signaling in the pathogenesis and treatment of myeloid malignancies. JAKSTAT 1, 55–64 (2012).

pubmed: 24058751 pmcid: 3670294

Geiger, J. L., Grandis, J. R. & Bauman, J. E. The STAT3 pathway as a therapeutic target in head and neck cancer: barriers and innovations. Oral. Oncol. 56, 84–92 (2016).

pubmed: 26733183 doi: 10.1016/j.oraloncology.2015.11.022

Suh, Y.-A., Jo, S.-Y., Lee, H.-Y. & Lee, C. Inhibition of IL-6/STAT3 axis and targeting Axl and Tyro3 receptor tyrosine kinases by apigenin circumvent taxol resistance in ovarian cancer cells. Int. J. Oncol. 46, 1405–1411 (2015).

pubmed: 25544427 doi: 10.3892/ijo.2014.2808

Ludwig, H., Nachbaur, D., Fritz, E., Krainer, M. & Huber, H. Interleukin-6 is a prognostic factor in multiple myeloma. Blood 77, 2794–2795 (1991).

pubmed: 2043775 doi: 10.1182/blood.V77.12.2794.2794

Chen, Y. et al. STAT3, a poor survival predicator, is associated with lymph node metastasis from breast cancer. J. Breast Cancer 16, 40–49 (2013).

pubmed: 23593080 pmcid: 3625768 doi: 10.4048/jbc.2013.16.1.40

Shahmarvand, N., Nagy, A., Shahryari, J. & Ohgami, R. S. Mutations in the signal transducer and activator of transcription family of genes in cancer. Cancer Sci. 109, 926–933 (2018).

pubmed: 29417693 pmcid: 5891179 doi: 10.1111/cas.13525

Hassel, J. C., Winnemöller, D., Schartl, M. & Wellbrock, C. STAT5 contributes to antiapoptosis in melanoma. Melanoma Res. 18, 378–385 (2008).

pubmed: 19011510 doi: 10.1097/CMR.0b013e32830ce7d7

Constantinescu, S. N., Girardot, M. & Pecquet, C. Mining for JAK–STAT mutations in cancer. Trends Biochem. Sci. 33, 122–131 (2008).

pubmed: 18291658 doi: 10.1016/j.tibs.2007.12.002

Teramo, A. et al. Intrinsic and extrinsic mechanisms contribute to maintain the JAK/STAT pathway aberrantly activated in T-type large granular lymphocyte leukemia. Blood 121, 3843–3854 (2013).

pubmed: 23515927 doi: 10.1182/blood-2012-07-441378

Rajala, H. L. M., Porkka, K., Maciejewski, J. P., Loughran, T. P. & Mustjoki, S. Uncovering the pathogenesis of large granular lymphocytic leukemia-novel STAT3 and STAT5b mutations. Ann. Med. 46, 114–122 (2014).

pubmed: 24512550 doi: 10.3109/07853890.2014.882105

Rajala, H. L. M. et al. Discovery of somatic STAT5b mutations in large granular lymphocytic leukemia. Blood 121, 4541–4550 (2013).

pubmed: 23596048 pmcid: 3668487 doi: 10.1182/blood-2012-12-474577

Crescenzo, R. et al. Convergent mutations and kinase fusions lead to oncogenic STAT3 activation in anaplastic large cell lymphoma. Cancer Cell 27, 516–532 (2015).

pubmed: 25873174 pmcid: 5898430 doi: 10.1016/j.ccell.2015.03.006

Ohgami, R. S., Ma, L., Monabati, A., Zehnder, J. L. & Arber, D. A. STAT3 mutations are present in aggressive B-cell lymphomas including a subset of diffuse large B-cell lymphomas with CD30 expression. Haematologica 99, 105–107 (2014).

doi: 10.3324/haematol.2013.101543

Ohgami, R. S. et al. STAT3 mutations are frequent in CD30+ T-cell lymphomas and T-cell large granular lymphocytic leukemia. Leukemia 27, 2244–2247 (2013).

pubmed: 23563237 doi: 10.1038/leu.2013.104

Arulogun, S. O. et al. JAK1 somatic mutation in a myeloproliferative neoplasm. Haematologica 102, 324–327 (2017).

doi: 10.3324/haematol.2017.170266

Mullighan, C. G. et al. JAK mutations in high-risk childhood acute lymphoblastic leukemia. Proc. Natl Acad. Sci. USA 106, 9414–9418 (2009).

pubmed: 19470474 pmcid: 2695045 doi: 10.1073/pnas.0811761106

Jeong, E. G. et al. Somatic mutations of JAK1 and JAK3 in acute leukemias and solid cancers. Clin. Cancer Res. 14, 3716–3721 (2008).

pubmed: 18559588 doi: 10.1158/1078-0432.CCR-07-4839

Flex, E. et al. Somatically acquired JAK1 mutations in adult acute lymphoblastic leukemia. J. Exp. Med. 205, 751–758 (2008).

pubmed: 18362173 pmcid: 2292215 doi: 10.1084/jem.20072182

Xiang, Z. et al. Identification of somatic JAK1 mutations in patients with acute myeloid leukemia. Blood 111, 4809–4812 (2008).

pubmed: 18160671 pmcid: 2343608 doi: 10.1182/blood-2007-05-090308

Kralovics, R. et al. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N. Engl. J. Med. 352, 1779–1790 (2005).

pubmed: 15858187 doi: 10.1056/NEJMoa051113

James, C. et al. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature 434, 1144–1148 (2005).

pubmed: 15793561 doi: 10.1038/nature03546

Haan, C., Behrmann, I. & Haan, S. Perspectives for the use of structural information and chemical genetics to develop inhibitors of Janus kinases. J. Cell Mol. Med. 14, 504–527 (2010).

pubmed: 20132407 pmcid: 3823453 doi: 10.1111/j.1582-4934.2010.01018.x

Mercher, T. et al. JAK2T875N is a novel activating mutation that results in myeloproliferative disease with features of megakaryoblastic leukemia in a murine bone marrow transplantation model. Blood 108, 2770–2779 (2006).

pubmed: 16804112 pmcid: 1895587 doi: 10.1182/blood-2006-04-014712

Malinge, S. et al. Activating mutations in human acute megakaryoblastic leukemia. Blood 112, 4220–4226 (2008).

pubmed: 18755984 doi: 10.1182/blood-2008-01-136366

Zhao, L. et al. A JAK2 interdomain linker relays Epo receptor engagement signals to kinase activation. J. Biol. Chem. 284, 26988–26998 (2009).

pubmed: 19638629 pmcid: 2785384 doi: 10.1074/jbc.M109.011387

Sayyah, J. et al. Z3, a novel Jak2 tyrosine kinase small-molecule inhibitor that suppresses Jak2-mediated pathologic cell growth. Mol. Cancer Ther. 7, 2308–2318 (2008).

pubmed: 18723478 pmcid: 2579271 doi: 10.1158/1535-7163.MCT-08-0279

Percy, M. J. et al. The frequency of JAK2 exon 12 mutations in idiopathic erythrocytosis patients with low serum erythropoietin levels. Haematologica 92, 1607–1614 (2007).

pubmed: 18055983 doi: 10.3324/haematol.11643

Pietra, D. et al. Somatic mutations of JAK2 exon 12 in patients with JAK2 (V617F)-negative myeloproliferative disorders. Blood 111, 1686–1689 (2008).

pubmed: 17984312 doi: 10.1182/blood-2007-07-101576

Schnittger, S. et al. Detection of JAK2 exon 12 mutations in 15 patients with JAK2V617F negative polycythemia vera. Haematologica 94, 414–418 (2009).

pubmed: 19252176 pmcid: 2649350 doi: 10.3324/haematol.13223

Zhang, S.-J. et al. The investigation of JAK2 mutation in Chinese myeloproliferative diseases-identification of a novel C616Y point mutation in a PV patient. Int. J. Lab. Hematol. 29, 71–72 (2007).

pubmed: 17224012 doi: 10.1111/j.1365-2257.2006.00864.x

Funakoshi-Tago, M. et al. The acute lymphoblastic leukemia-associated JAK2 L611S mutant induces tumorigenesis in nude mice. J. Biol. Chem. 284, 12680–12690 (2009).

pubmed: 19289461 pmcid: 2675997 doi: 10.1074/jbc.M808879200

Gaikwad, A. et al. Prevalence and clinical correlates of JAK2 mutations in Down syndrome acute lymphoblastic leukaemia. Br. J. Haematol. 144, 930–932 (2009).

pubmed: 19120350 doi: 10.1111/j.1365-2141.2008.07552.x

Bercovich, D. et al. Mutations of JAK2 in acute lymphoblastic leukaemias associated with Down’s syndrome. Lancet 372, 1484–1492 (2008).

pubmed: 18805579 doi: 10.1016/S0140-6736(08)61341-0

Degryse, S. et al. Mutant JAK3 signaling is increased by loss of wild-type JAK3 or by acquisition of secondary JAK3 mutations in T-ALL. Blood 131, 421–425 (2018).

pubmed: 29187379 pmcid: 5796683 doi: 10.1182/blood-2017-07-797597

Walters, D. K. et al. Activating alleles of JAK3 in acute megakaryoblastic leukemia. Cancer Cell 10, 65–75 (2006).

pubmed: 16843266 doi: 10.1016/j.ccr.2006.06.002

Sato, T. et al. Functional analysis of JAK3 mutations in transient myeloproliferative disorder and acute megakaryoblastic leukaemia accompanying Down syndrome. Br. J. Haematol. 141, 681–688 (2008).

pubmed: 18397343 doi: 10.1111/j.1365-2141.2008.07081.x

De Vita, S. et al. Loss-of-function JAK3 mutations in TMD and AMKL of Down syndrome. Br. J. Haematol. 137, 337–341 (2007).

pubmed: 17456055 doi: 10.1111/j.1365-2141.2007.06574.x

Kiyoi, H., Yamaji, S., Kojima, S. & Naoe, T. JAK3 mutations occur in acute megakaryoblastic leukemia both in Down syndrome children and non-Down syndrome adults. Leukemia 21, 574–576 (2007).

pubmed: 17252020 doi: 10.1038/sj.leu.2404527

Kuravi, S. et al. Functional characterization of NPM1–TYK2 fusion oncogene. NPJ Precis. Oncol. 6 (2022).

Tomasson, M. H. et al. Somatic mutations and germline sequence variants in the expressed tyrosine kinase genes of patients with de novo acute myeloid leukemia. Blood 111, 4797–4808 (2008).

pubmed: 18270328 pmcid: 2343607 doi: 10.1182/blood-2007-09-113027

Li, Z., Rotival, M., Patin, E., Michel, F. & Pellegrini, S. Two common disease-associated TYK2 variants impact exon splicing and TYK2 dosage. PLoS One 15, 1–20 (2020).

Peters, T. L. et al. Intrinsic resistance to ROS1 inhibition in a patient with CD74-ROS1 mediated by AXL overexpression. Thorac. Cancer 14, 3259–3265 (2023).

pubmed: 37727007 pmcid: 10665781 doi: 10.1111/1759-7714.15116

Breitenecker, K. et al. Synergism of the receptor tyrosine kinase Axl with ErbB receptors mediates resistance to regorafenib in hepatocellular carcinoma. Front Oncol 13 (2023).

Volta, F. et al. Intrinsic resistance to osimertinib in EGFR mutated NSCLC cell lines induced by alteration in cell-cycle regulators. Target Oncol. 18, 953–964 (2023).

pubmed: 37855989 pmcid: 10663255 doi: 10.1007/s11523-023-01005-0

Parseghian, C. M., Napolitano, S., Loree, J. M. & Kopetz, S. Mechanisms of innate and acquired resistance to anti-EGFR therapy: a review of current knowledge with a focus on rechallenge therapies. Clin. Cancer Res. 25, 6899–6908 (2019).

pubmed: 31263029 pmcid: 6891150 doi: 10.1158/1078-0432.CCR-19-0823

Venook, A. P. et al. Effect of first-line chemotherapy combined with cetuximab or bevacizumab on overall survival in patients with KRAS wild-type advanced or metastatic colorectal cancer: a randomized clinical trial. JAMA 317, 2392–2401 (2017).

pubmed: 28632865 pmcid: 5545896 doi: 10.1001/jama.2017.7105

Yang, Y., Li, S., Wang, Y., Zhao, Y. & Li, Q. Protein tyrosine kinase inhibitor resistance in malignant tumors: molecular mechanisms and future perspective. Signal. Transduct. Target. Ther. 7, 1–36 (2022).

Zhu, X. et al. Identification and validation of afatinib potential drug resistance gene BIRC5 in non-small cell lung cancer. Front. Oncol. 11 (2021).

Del Re, M. et al. Implications of KRAS mutations in acquired resistance to treatment in NSCLC. Oncotarget 9, 6630–6643 (2018).

pubmed: 29464099 doi: 10.18632/oncotarget.23553

Riedel, R. et al. Resistance to MET inhibition in MET-dependent NSCLC and therapeutic activity after switching from type I to type II MET inhibitors. Eur. J. Cancer 179, 124–135 (2023).

pubmed: 36521334 doi: 10.1016/j.ejca.2022.11.010

Wang, L.-S. et al. Acquired EML4-ALK fusion and EGFR C797S in cis mutation as resistance mechanisms to osimertinib in a non-small cell lung cancer patient with EGFR L858R/T790M. Anticancer Drugs 34, 1146–1150 (2023).

pubmed: 36728908 doi: 10.1097/CAD.0000000000001489

Fukuda, S. et al. The magnitude of CXCR4 signaling regulates resistance to quizartinib in FLT3/ITD+ cells via RUNX1. Leuk. Res. 124 (2023).

Gomatou, G., Syrigos, N. & Kotteas, E. Osimertinib resistance: molecular mechanisms and emerging treatment options. Cancers 15 (2023).

Xia, W. et al. Resistance to ErbB2 tyrosine kinase inhibitors in breast cancer is mediated by calcium-dependent activation of RelA. Mol. Cancer Ther. 9, 292–299 (2010).

pubmed: 20124457 doi: 10.1158/1535-7163.MCT-09-1041

Politi, K., Fan, P.-D., Shen, R., Zakowski, M. & Varmus, H. Erlotinib resistance in mouse models of epidermal growth factor receptor-induced lung adenocarcinoma. Dis. Model Mech. 3, 111–119 (2010).

pubmed: 20007486 doi: 10.1242/dmm.003681

Katayama, R. et al. Mechanisms of acquired crizotinib resistance in ALK-rearranged lung Cancers. Sci. Transl. Med. 4, 120ra17–120ra17 (2012).

pubmed: 22277784 pmcid: 3385512 doi: 10.1126/scitranslmed.3003316

Yoshida, T. et al. Tyrosine phosphoproteomics identifies both codrivers and cotargeting strategies for T790M-related EGFR-TKI resistance in non-small cell lung cancer. Clin. Cancer Res. 20, 4059–4074 (2014).

pubmed: 24919575 pmcid: 4119578 doi: 10.1158/1078-0432.CCR-13-1559

Pang, L.-L. et al. Efficacy and potential resistance mechanisms of afatinib in advanced non-small cell lung cancer patients with EGFR G719X/L861Q/S768I. Cancer 128, 3804–3814 (2022).

pubmed: 36069292 doi: 10.1002/cncr.34451

Nakamura, T. et al. Mechanisms of acquired resistance to afatinib clarified with liquid biopsy. PLoS One 13 (2018).

Reischmann, N. et al. Overcoming MET-mediated resistance in oncogene-driven NSCLC. iScience 26, 1–20 (2023).

Kong, W.-M., Guo, Y.-J., Ma, J. & Shi, C. BTN2A1-BRAF fusion may be a novel mechanism of resistance to osimertinib in lung adenocarcinoma: a case report. Transl. Cancer Res. 12, 186–193 (2023).

pubmed: 36760378 pmcid: 9906054 doi: 10.21037/tcr-22-2060

Mazières, J. et al. Lung cancer that harbors an HER2 mutation: epidemiologic characteristics and therapeutic perspectives. J. Clin. Oncol. 31, 1997–2003 (2013).

pubmed: 23610105 doi: 10.1200/JCO.2012.45.6095

Peng, Y. & Tan, J. The relationship between IGF pathway and acquired resistance to tyrosine kinase inhibitors in cancer therapy. Front. Biosci. (Landmark Ed.) 28 (2023).

de Reyniès, A., Boige, V., Milano, G., Faivre, J. & Laurent-Puig, P. KRAS mutation signature in colorectal tumors significantly overlaps with the cetuximab response signature. J. Clin. Oncol. 26, 2228–2230 (2008).

pubmed: 18445856 doi: 10.1200/JCO.2007.15.9186

Liu, D., Lu, X., Huang, W. & Zhuang, W. Long non-coding RNAs in non-small cell lung cancer: implications for EGFR-TKI resistance. Front. Genet. 14 (2023).

Nguyen, K.-S. H., Kobayashi, S. & Costa, D. B. Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancers dependent on the epidermal growth factor receptor pathway. Clin. Lung Cancer 10, 281–289 (2009).

pubmed: 19632948 pmcid: 2758558 doi: 10.3816/CLC.2009.n.039

Lin, X. et al. KIAA1429 promotes tumorigenesis and gefitinib resistance in lung adenocarcinoma by activating the JNK/MAPK pathway in an m6A-dependent manner. Drug Resist. Updat. 66, 1–12 (2023).

Bugide, S., Edwards, Y. J. K., Gupta, R., Green, M. R. & Wajapeyee, N. CBX5 loss drives EGFR inhibitor resistance and results in therapeutically actionable vulnerabilities in lung cancer. Proc Natl Acad. Sci. USA 120 (2023).

de Miguel, F. J. et al. Mammalian SWI/SNF chromatin remodeling complexes promote tyrosine kinase inhibitor resistance in EGFR-mutant lung cancer. Cancer Cell 41, 1516–1534 (2023).

pubmed: 37541244 doi: 10.1016/j.ccell.2023.07.005

Chen, H. et al. Long noncoding RNA RP11-89K21.1 interacts with miR-146a/b-5p to promote proliferation and gefitinib resistance through regulating RHPN2 and RhoA/ROCK pathway in lung adenocarcinoma. Cancer Biother. Radiopharm. 38, 282–292 (2023).

pubmed: 33877886

Cheng, D. et al. Exosomal non-coding RNAs-mediated EGFR-TKIs resistance in NSCLC with EGFR mutation. Med. Oncol. 40 (2023).

Azuma, K. et al. FGFR1 activation is an escape mechanism in human lung cancer cells resistant to afatinib, a pan-EGFR family kinase inhibitor. Oncotarget 5, 5908–5919 (2014).

pubmed: 25115383 pmcid: 4171601 doi: 10.18632/oncotarget.1866

Ren, S. et al. The pseudogene DUXAP10 contributes to gefitinib resistance in NSCLC by repressing OAS2 expression. Acta Biochim. Biophys. Sin. 55, 81–90 (2023).

pubmed: 36471952

Wen, C. et al. CircSETD3 mediates acquired resistance to gefitinib in non-small lung cancer cells by FXR1/ECT2 pathway. Int. J. Biochem. Cell Biol. 154 (2023).

Zhang, Z. et al. Activation of the AXL kinase causes resistance to EGFR-targeted therapy in lung cancer. Nat. Genet. 44, 852–860 (2012).

pubmed: 22751098 pmcid: 3408577 doi: 10.1038/ng.2330

Huang, S. et al. p53 modulates acquired resistance to EGFR inhibitors and radiation. Cancer Res. 71, 7071–7079 (2011).

pubmed: 22068033 pmcid: 3229180 doi: 10.1158/0008-5472.CAN-11-0128

Takahashi, H. et al. Notch pathway regulates osimertinib drug-tolerant persistence in EGFR-mutated non-small-cell lung cancer. Cancer Sci. 114, 1635–1650 (2023).

pubmed: 36411521 doi: 10.1111/cas.15674

Baumgart, A. et al. ADAM17 regulates epidermal growth factor receptor expression through the activation of Notch1 in non-small cell lung cancer. Cancer Res. 70, 5368–5378 (2010).

pubmed: 20551051 doi: 10.1158/0008-5472.CAN-09-3763

Chen, X. et al. Crizotinib overcomes hepatocyte growth factor-mediated resistance to gefitinib in EGFR-mutant non-small-cell lung cancer cells. Anticancer Drugs 24, 1039–1046 (2013).

pubmed: 23962905 doi: 10.1097/CAD.0000000000000011

van der Wekken, A. J. et al. Resistance mechanisms after tyrosine kinase inhibitors afatinib and crizotinib in non-small cell lung cancer, a review of the literature. Crit. Rev. Oncol. Hematol. 100, 107–116 (2016).

pubmed: 26852079 doi: 10.1016/j.critrevonc.2016.01.024

Kim, H. R. et al. Epithelial-mesenchymal transition leads to crizotinib resistance in H2228 lung cancer cells with EML4-ALK translocation. Mol. Oncol. 7, 1093–1102 (2013).

pubmed: 23993685 pmcid: 5528442 doi: 10.1016/j.molonc.2013.08.001

Lee, K.-L. et al. Sustaining the activation of EGFR signal by inflammatory cytokine IL17A prompts cell proliferation and EGFR-TKI resistance in lung cancer. Cancers (Basel) 15, 1–18 (2023).

Kim, S. M. et al. Activation of IL-6R/JAK1/STAT3 signaling induces de novo resistance to irreversible EGFR inhibitors in non-small cell lung cancer with T790M resistance mutation. Mol. Cancer Ther. 11, 2254–2264 (2012).

pubmed: 22891040 doi: 10.1158/1535-7163.MCT-12-0311

Katayama, Y. et al. Adaptive resistance to lorlatinib via EGFR signaling in ALK-rearranged lung cancer. NPJ Precis. Oncol. 7 (2023).

Kondo, N. et al. MIG6 loss confers resistance to ALK/ROS1 inhibitors in NSCLC through EGFR activation by low-dose EGF. JCI Insight 8 (2023).

Liu, W.-J. et al. Elevated NOX4 promotes tumorigenesis and acquired EGFR-TKIs resistance via enhancing IL-8/PD-L1 signaling in NSCLC. Drug Resist. Updat. 70 (2023).

Romaniello, D. et al. Targeting HER3, a catalytically defective receptor tyrosine kinase, prevents resistance of lung cancer to a third-generation EGFR kinase inhibitor. Cancers 12 (2020).

Sang, J. et al. Targeted inhibition of the molecular chaperone Hsp90 overcomes ALK inhibitor resistance in non-small cell lung cancer. Cancer Discov. 3, 430–443 (2013).

pubmed: 23533265 pmcid: 4086149 doi: 10.1158/2159-8290.CD-12-0440

He, M. et al. Sunitinib increases the cancer stem cells and vasculogenic mimicry formation via modulating the lncRNA-ECVSR/ERβ/Hif2-α signaling. Cancer Lett. 524, 15–28 (2022).

pubmed: 34461182 doi: 10.1016/j.canlet.2021.08.028

Coco, S. et al. Afatinib resistance in non-small cell lung cancer involves the PI3K/AKT and MAPK/ERK signalling pathways and epithelial-to-mesenchymal transition. Target Oncol. 10, 393–404 (2015).

pubmed: 25341405 doi: 10.1007/s11523-014-0344-7

Hammers, H. J. et al. Reversible epithelial to mesenchymal transition and acquired resistance to sunitinib in patients with renal cell carcinoma: evidence from a xenograft study. Mol. Cancer Ther. 9, 1525–1535 (2010).

pubmed: 20501804 pmcid: 3049816 doi: 10.1158/1535-7163.MCT-09-1106

Goel, S. et al. Overcoming therapeutic resistance in HER2-positive breast cancers with CDK4/6 inhibitors. Cancer Cell 29, 255–269 (2016).

pubmed: 26977878 pmcid: 4794996 doi: 10.1016/j.ccell.2016.02.006

Liu, Y., Li, C., Lu, Y., Liu, C. & Yang, W. Tumor microenvironment-mediated immune tolerance in development and treatment of gastric cancer. Front. Immunol. 13, 1–17 (2022).

Terry, S. et al. Hypoxia-driven intratumor heterogeneity and immune evasion. Cancer Lett. 492, 1–10 (2020).

pubmed: 32712233 doi: 10.1016/j.canlet.2020.07.004

Lee, J. et al. Genomic landscape of acquired resistance to third-generation EGFR tyrosine kinase inhibitors in EGFR T790M-mutant non-small cell lung cancer. Cancer 126, 2704–2712 (2020).

pubmed: 32154925 doi: 10.1002/cncr.32809

Filippi, I., Naldini, A. & Carraro, F. Role of the hypoxic microenvironment in the antitumor activity of tyrosine kinase inhibitors. Curr. Med. Chem. 18, 2885–2892 (2011).

pubmed: 21651491 doi: 10.2174/092986711796150540

Bixby, D. & Talpaz, M. Mechanisms of resistance to tyrosine kinase inhibitors in chronic myeloid leukemia and recent therapeutic strategies to overcome resistance. Hematology 2009, 461–476 (2009).

doi: 10.1182/asheducation-2009.1.461

Bridgeman, V. L. et al. Vessel co-option is common in human lung metastases and mediates resistance to anti-angiogenic therapy in preclinical lung metastasis models. J. Pathol. 241, 362–374 (2017).

pubmed: 27859259 doi: 10.1002/path.4845

Kuczynski, E. A. & Reynolds, A. R. Vessel co-option and resistance to anti-angiogenic therapy. Angiogenesis 23, 55–74 (2020).

pubmed: 31865479 doi: 10.1007/s10456-019-09698-6

Xie, X. et al. OSGIN1 is a novel TUBB3 regulator that promotes tumor progression and gefitinib resistance in non-small cell lung cancer. Cell Mol. Life Sci. 80 (2023).

Chen, Y.-H., Yang, Y., Xu, L.-J., Deng, Y. & Fu, J.-W. Regulation of epidermal growth factor receptor tyrosine kinase inhibitor resistance via Ambra1-mediated autophagy in non-small cell lung cancer. J. Physiol. Pharm. 74, 325–334 (2023).

Giuliano, M. et al. Upregulation of ER signaling as an adaptive mechanism of cell survival in HER2-positive breast tumors treated with anti-HER2 therapy. Clin. Cancer Res. 21, 3995–4003 (2015).

pubmed: 26015514 pmcid: 4558260 doi: 10.1158/1078-0432.CCR-14-2728

Xiao, Z., Li, M., Zhang, X., Rong, X. & Xu, H. TRIP13 overexpression promotes gefitinib resistance in non-small cell lung cancer via regulating autophagy and phosphorylation of the EGFR signaling pathway. Oncol. Rep. 49 (2023).

Watson, S. S. et al. Microenvironment-mediated mechanisms of resistance to HER2 inhibitors differ between HER2+ breast cancer subtypes. Cell Syst. 6, 329–342 (2018).

pubmed: 29550255 pmcid: 5927625 doi: 10.1016/j.cels.2018.02.001

Ji, C. et al. Induction of autophagy contributes to crizotinib resistance in ALK-positive lung cancer. Cancer Biol. Ther. 15, 570–577 (2014).

pubmed: 24556908 pmcid: 4026079 doi: 10.4161/cbt.28162

Dai, J. et al. LncRNA LINC00969 promotes acquired gefitinib resistance by epigenetically suppressing of NLRP3 at transcriptional and posttranscriptional levels to inhibit pyroptosis in lung cancer. Cell Death Dis. 14 (2023).

Lee, T.-G., Jeong, E.-H., Kim, S. Y., Kim, H.-R. & Kim, C. H. The combination of irreversible EGFR TKIs and SAHA induces apoptosis and autophagy-mediated cell death to overcome acquired resistance in EGFR T790M-mutated lung cancer. Int. J. Cancer 136, 2717–2729 (2015).

pubmed: 25382705 doi: 10.1002/ijc.29320

Zhang, W. et al. Concomitant targeting of FLT3 and BTK overcomes FLT3 inhibitor resistance in acute myeloid leukemia through the inhibition of autophagy. Haematologica 108, 1500–1514 (2023).

pubmed: 36226489 doi: 10.3324/haematol.2022.280884

Chen, R. et al. Modulation of the tumour microenvironment in hepatocellular carcinoma by tyrosine kinase inhibitors: from modulation to combination therapy targeting the microenvironment. Cancer Cell Int. 22 (2022).

Noel, B. M. et al. Multiomic profiling of tyrosine kinase inhibitor-resistant K562 cells suggests metabolic reprogramming to promote cell survival. J. Proteome Res. 18, 1842–1856 (2019).

pubmed: 30730747 pmcid: 7250065 doi: 10.1021/acs.jproteome.9b00028

Huang, F. et al. SLC12A8 mediates TKI resistance in EGFR-mutant lung cancer via PDK1/AKT axis. J. Cancer Res. Clin. Oncol. 149, 16729–16739 (2023).

pubmed: 37725242 doi: 10.1007/s00432-023-05416-4

Su, S.-F. et al. Genome-wide epigenetic landscape of lung adenocarcinoma links HOXB9 DNA methylation to intrinsic EGFR-TKI resistance and heterogeneous responses. JCO Precis. Oncol. 5, 418–431 (2021).

doi: 10.1200/PO.20.00151

de Klerk, D. J., Honeywell, R. J., Jansen, G. & Peters, G. J. Transporter and lysosomal mediated (Multi)drug resistance to tyrosine kinase inhibitors and potential strategies to overcome resistance. Cancers 10 (2018).

Chhouri, H., Alexandre, D. & Grumolato, L. Mechanisms of acquired resistance and tolerance to EGFR targeted therapy in non-small cell lung cancer. Cancers 15 (2023).

Adelaiye-Ogala, R. et al. EZH2 modifies sunitinib resistance in renal cell carcinoma by kinome reprogramming. Cancer Res. 77, 6651–6666 (2017).

pubmed: 28978636 pmcid: 5712262 doi: 10.1158/0008-5472.CAN-17-0899

Ghiaur, G. & Levis, M. Mechanisms of resistance to FLT3 inhibitors and the role of the bone marrow microenvironment. Hematol. Oncol. Clin. North Am. 31, 681–692 (2017).

pubmed: 28673395 pmcid: 5512588 doi: 10.1016/j.hoc.2017.04.005

Ouar, Z., Lacave, R., Bens, M. & Vandewalle, A. Mechanisms of altered sequestration and efflux of chemotherapeutic drugs by multidrug-resistant cells. Cell Biol. Toxicol. 15, 91–100 (1999).

pubmed: 10408356 doi: 10.1023/A:1007521430236

Mlejnek, P. What is the significance of lysosomal-mediated resistance to imatinib? Cells 12, 1–15 (2023).

doi: 10.3390/cells12050709

Locher, K. P. Mechanistic diversity in ATP-binding cassette (ABC) transporters. Nat. Struct. Mol. Biol. 23, 487–493 (2016).

pubmed: 27273632 doi: 10.1038/nsmb.3216

Lu, J. et al. Reprogramming of TAMs via the STAT3/CD47-SIRPα axis promotes acquired resistance to EGFR-TKIs in lung cancer. Cancer Lett. 564 (2023).

Lin, L., Yee, S. W., Kim, R. B. & Giacomini, K. M. SLC transporters as therapeutic targets: emerging opportunities. Nat. Rev. Drug Discov. 14, 543–560 (2015).

pubmed: 26111766 pmcid: 4698371 doi: 10.1038/nrd4626

Diekstra, M. H. M. et al. CYP3A5 and ABCB1 polymorphisms as predictors for sunitinib outcome in metastatic renal cell carcinoma. Eur. Urol. 68, 621–629 (2015).

pubmed: 25930089 doi: 10.1016/j.eururo.2015.04.018

Chen, S. et al. Changes of tumor microenvironment in non-small cell lung cancer after TKI treatments. Front. Immunol. 14, 1094764 (2023).

Cheng, D. et al. Tumor-associated macrophages mediate resistance of EGFR-TKIs in non-small cell lung cancer: mechanisms and prospects. Front. Immunol. 14, 1–12 (2023).

Zhao, B., Zhang, Y., Lu, S. & Li, M. Macrophage renewal modes affect acquired resistance to gefitinib in EGFR-mutant lung cancer PC-9 cells. Oncol. Rep. 49 (2023).

Jeong, J. et al. Downregulation of AP1S1 causes the lysosomal degradation of EGFR in non-small cell lung cancer. J. Cell Physiol. 238, 2335–2347 (2023).

pubmed: 37659097 doi: 10.1002/jcp.31112

Soverini, S., Mancini, M., Bavaro, L., Cavo, M. & Martinelli, G. Chronic myeloid leukemia: the paradigm of targeting oncogenic tyrosine kinase signaling and counteracting resistance for successful cancer therapy. Mol. Cancer 17, 1–15 (2018).

Shyam Sunder, S., Sharma, U. C. & Pokharel, S. Adverse effects of tyrosine kinase inhibitors in cancer therapy: pathophysiology, mechanisms and clinical management. Signal. Transduct. Target. Ther. 8 (2023).

Dobbin, S. J. H., Petrie, M. C., Myles, R. C., Touyz, R. M. & Lang, N. N. Cardiotoxic effects of angiogenesis inhibitors. Clin. Sci. 135, 71–100 (2021).

doi: 10.1042/CS20200305

Sundararajan, S., Kumar, A., Poongkunran, M., Kannan, A. & Vogelzang, N. J. Cardiovascular adverse effects of targeted antiangiogenic drugs: mechanisms and management. Future Oncol. 12, 1067–1080 (2016).

pubmed: 26901457 doi: 10.2217/fon.16.4

Du, X. L., Xia, R., Burau, K. & Liu, C.-C. Cardiac risk associated with the receipt of anthracycline and trastuzumab in a large nationwide cohort of older women with breast cancer, 1998-2005. Med. Oncol. 28, 80–90 (2011).

doi: 10.1007/s12032-010-9717-7

Curigliano, G. et al. Management of cardiac disease in cancer patients throughout oncological treatment: ESMO consensus recommendations. Ann. Oncol. 31, 171–190 (2020).

pubmed: 31959335 doi: 10.1016/j.annonc.2019.10.023

Pinkhas, D., Ho, T. & Smith, S. Assessment of pazopanib-related hypertension, cardiac dysfunction and identification of clinical risk factors for their development. Cardiooncology 3 (2017).

Chang, H.-M., Moudgil, R., Scarabelli, T., Okwuosa, T. M. & Yeh, E. T. H. Cardiovascular complications of cancer therapy: best practices in diagnosis, prevention, and management: part 1. J. Am. Coll. Cardiol. 70, 2536–2551 (2017).

pubmed: 29145954 pmcid: 5825187 doi: 10.1016/j.jacc.2017.09.1096

Díaz-Serrano, A., Gella, P., Jiménez, E., Zugazagoitia, J. & Paz-Ares Rodríguez, L. Targeting EGFR in lung cancer: current standards and developments. Drugs 78, 893–911 (2018).

pubmed: 29915896 doi: 10.1007/s40265-018-0916-4

Wang, L. & Wang, W. Safety and efficacy of anaplastic lymphoma kinase tyrosine kinase inhibitors in non-small cell lung cancer (Review). Oncol. Rep. 45, 13–28 (2021).

pubmed: 33200229

Godinas, L. et al. Tyrosine kinase inhibitors in pulmonary arterial hypertension: a double-edge sword? Semin. Respir. Crit. Care Med. 34, 714–724 (2013).

pubmed: 24037637 doi: 10.1055/s-0033-1356494

Montani, D. et al. Pulmonary arterial hypertension in patients treated by dasatinib. Circulation 125, 2128–2137 (2012).

pubmed: 22451584 doi: 10.1161/CIRCULATIONAHA.111.079921

Giudice, V., Vecchione, C. & Selleri, C. Cardiotoxicity of novel targeted hematological therapies. Life 10, (2020).

Mishra, A. K., Sahu, K. K., Kaul, S. & Lal, A. Dasatinib induced pleuro-pericardial effusion. Acta Biomed. 91, 142–143 (2020).

pubmed: 32191670 pmcid: 7569591

Maroun, J. A. et al. Prevention and management of chemotherapy-induced diarrhea in patients with colorectal cancer: a consensus statement by the Canadian Working Group on Chemotherapy-Induced Diarrhea. Curr. Oncol. 14, 13–20 (2007).

pubmed: 17576459 pmcid: 1891194 doi: 10.3747/co.2007.96

Wang, Z. et al. Comparison of hepatotoxicity associated with new BCR-ABL tyrosine kinase inhibitors vs imatinib among patients with chronic myeloid leukemia: a systematic review and meta-analysis. JAMA Netw. Open 4 (2021).

Nelson, R. P. et al. Desensitization to imatinib in patients with leukemia. Ann. Allergy Asthma Immunol. 97, 216–222 (2006).

pubmed: 16937754 doi: 10.1016/S1081-1206(10)60016-6

Zheng, P.-P., Li, J. & Kros, J. M. Breakthroughs in modern cancer therapy and elusive cardiotoxicity: Critical research-practice gaps, challenges, and insights. Med Res. Rev. 38, 325–376 (2018).

pubmed: 28862319 doi: 10.1002/med.21463

Hamberg, P. et al. Non-islet-cell tumor induced hypoglycemia in patients with advanced gastrointestinal stromal tumor possibly worsened by imatinib. J. Clin. Oncol. 24, 30–31 (2006).

doi: 10.1200/JCO.2006.06.5318

Lodish, M. B. & Stratakis, C. A. Endocrine side effects of broad-acting kinase inhibitors. Endocr. Relat. Cancer 17, 233–244 (2010).

doi: 10.1677/ERC-10-0082

Torino, F., Corsello, S. M., Longo, R., Barnabei, A. & Gasparini, G. Hypothyroidism related to tyrosine kinase inhibitors: an emerging toxic effect of targeted therapy. Nat. Rev. Clin. Oncol. 6, 219–228 (2009).

pubmed: 19333228 doi: 10.1038/nrclinonc.2009.4

Pezzilli, R., Corinaldesi, R. & Morselli-Labate, A. M. Tyrosine kinase inhibitors and acute pancreatitis. JOP 11, 291–293 (2010).

pubmed: 20442535

Suh, C. H. et al. Pneumonitis in advanced non-small-cell lung cancer patients treated with EGFR tyrosine kinase inhibitor: Meta-analysis of 153 cohorts with 15,713 patients: meta-analysis of incidence and risk factors of EGFR-TKI pneumonitis in NSCLC. Lung Cancer 123, 60–69 (2018).

pubmed: 30089596 doi: 10.1016/j.lungcan.2018.06.032

Kanemura, H., Takeda, M., Shimizu, S. & Nakagawa, K. Interstitial lung disease associated with capmatinib therapy in a patient with non-small cell lung cancer harboring a skipping mutation of MET exon 14. Thorac. Cancer 12, 549–552 (2021).

pubmed: 33347701 doi: 10.1111/1759-7714.13790

Cabanillas, M. E., Hu, M. I., Durand, J.-B. & Busaidy, N. L. Challenges associated with tyrosine kinase inhibitor therapy for metastatic thyroid cancer. J. Thyroid Res. 2011, 1–9 (2011).

Kandula, P. & Agarwal, R. Proteinuria and hypertension with tyrosine kinase inhibitors. Kidney Int. 80, 1271–1277 (2011).

pubmed: 21900879 doi: 10.1038/ki.2011.288

Fachi, M. M. et al. Haematological adverse events associated with tyrosine kinase inhibitors in chronic myeloid leukaemia: a network meta-analysis. Br. J. Clin. Pharm. 85, 2280–2291 (2019).

doi: 10.1111/bcp.13933

Jabbour, E., Deininger, M. & Hochhaus, A. Management of adverse events associated with tyrosine kinase inhibitors in the treatment of chronic myeloid leukemia. Leukemia 25, 201–210 (2011).

pubmed: 20861918 doi: 10.1038/leu.2010.215

Hakkola, J., Hukkanen, J., Turpeinen, M. & Pelkonen, O. Inhibition and induction of CYP enzymes in humans: an update. Arch. Toxicol. 94, 3671–3722 (2020).

pubmed: 33111191 pmcid: 7603454 doi: 10.1007/s00204-020-02936-7

Rambhatla, A., Strug, M. R., De Paredes, J. G., Cordoba Munoz, M. I. & Thakur, M. Fertility considerations in targeted biologic therapy with tyrosine kinase inhibitors: a review. J. Assist. Reprod. Genet. 38, 1897–1908 (2021).

pubmed: 33826052 pmcid: 8417172 doi: 10.1007/s10815-021-02181-6

Dou, X., Qin, Y., Huang, X. & Jiang, Q. Planned pregnancy in female patients with chronic myeloid leukemia receiving tyrosine kinase inhibitor therapy. Oncologist 24, 1141–1147 (2019).

doi: 10.1634/theoncologist.2019-0109

Hua, G. et al. Real-world circulating tumor DNA analysis depicts resistance mechanism and clonal evolution in ALK inhibitor-treated lung adenocarcinoma patients. ESMO Open 7 (2022).

Choi, Y.-R. et al. Early On-treatment prediction of the mechanisms of acquired resistance to EGFR tyrosine kinase inhibitors. Cancers 14 (2022).

Gorachinov, F. et al. Nanotechnology—a robust tool for fighting the challenges of drug resistance in non-small cell lung cancer. Beilstein J. Nanotechnol. 14, 240–261 (2023).

pubmed: 36865093 pmcid: 9972888 doi: 10.3762/bjnano.14.23

Shaurova, T. et al. A nanotherapeutic strategy to target drug-tolerant cells and overcome EGFR tyrosine kinase inhibitor resistance in lung cancer. Cancer Commun. 43, 503–507 (2023).

doi: 10.1002/cac2.12401

Lu, X. et al. Afatinib-loaded immunoliposomes functionalized with cetuximab: a novel strategy targeting the epidermal growth factor receptor for treatment of non-small-cell lung cancer. Int. J. Pharm. 560, 126–135 (2019).

pubmed: 30742982 doi: 10.1016/j.ijpharm.2019.02.001

Wan, X., Zheng, X., Pang, X., Zhang, Z. & Zhang, Q. Incorporation of lapatinib into human serum albumin nanoparticles with enhanced anti-tumor effects in HER2-positive breast cancer. Colloids Surf. B Biointerfaces 136, 817–827 (2015).

pubmed: 26539808 doi: 10.1016/j.colsurfb.2015.10.018

Han, W. et al. A nanomedicine approach enables co-delivery of cyclosporin A and gefitinib to potentiate the therapeutic efficacy in drug-resistant lung cancer. Signal Transduct. Target. Ther. 3 (2018).

Greish, K. et al. Micellar formulations of Crizotinib and Dasatinib in the management of glioblastoma multiforme. J. Drug Target. 26, 692–708 (2018).

pubmed: 29251531 doi: 10.1080/1061186X.2017.1419357

Smidova, V. et al. Nanomedicine of tyrosine kinase inhibitors. Theranostics 11, 1546–1567 (2021).

pubmed: 33408767 pmcid: 7778595 doi: 10.7150/thno.48662

Nilsson, M. B. et al. CD70 is a therapeutic target upregulated in EMT-associated EGFR tyrosine kinase inhibitor resistance. Cancer Cell 41, 340–355 (2023).

pubmed: 36787696 pmcid: 10259078 doi: 10.1016/j.ccell.2023.01.007

Desai, A. & Lovly, C. M. Strategies to overcome resistance to ALK inhibitors in non-small cell lung cancer: a narrative review. Transl. Lung Cancer Res. 12, 615–628 (2023).

pubmed: 37057106 pmcid: 10087990 doi: 10.21037/tlcr-22-708

Talwelkar, S. S. et al. PI3Kβ inhibition enhances ALK-inhibitor sensitivity in ALK-rearranged lung cancer. Mol. Oncol. 17, 747–764 (2023).

pubmed: 36423211 pmcid: 10158778 doi: 10.1002/1878-0261.13342

Sun, L. et al. Understanding and targeting the epigenetic regulation to overcome EGFR-TKIs resistance in human. Cancer Recent Pat. Anticancer Drug Discov. 18, 506–516 (2023).

pubmed: 36464873 doi: 10.2174/1574892818666221201145810

Yochum, Z. A. et al. Targeting the EMT transcription factor TWIST1 overcomes resistance to EGFR inhibitors in EGFR-mutant non-small-cell lung cancer. Oncogene 38, 656–670 (2019).

pubmed: 30171258 doi: 10.1038/s41388-018-0482-y

Qin, A. et al. Tyrosine kinase signaling-independent MET-targeting with CAR-T cells. J. Transl. Med. 21 (2023).

Camidge, D. R. et al. Phase Ib study of telisotuzumab vedotin in combination with erlotinib in patients with c-met protein–expressing non–small-cell lung cancer. J. Clin. Oncol. 41, 1105–1115 (2023).

pubmed: 36288547 doi: 10.1200/JCO.22.00739

Larcombe-Young, D., Papa, S. & Maher, J. PanErbB-targeted CAR T-cell immunotherapy of head and neck cancer. Expert Opin. Biol. Ther. 20, 965–970 (2020).

pubmed: 32567382 doi: 10.1080/14712598.2020.1786531

Chicas-Sett, R., Castilla Martinez, J., Hernández Blanquisett, A., Zafra, J. & Pastor-Peidro, J. Stereotactic ablative radiotherapy for acquired resistance to EGFR therapy in metastatic non-small cell lung cancer. Front. Oncol. 12 (2022).

Jiang, K. et al. Dual inhibition of CHK1/FLT3 enhances cytotoxicity and overcomes adaptive and acquired resistance in FLT3-ITD acute myeloid leukemia. Leukemia 37, 539–549 (2023).

pubmed: 36526736 doi: 10.1038/s41375-022-01795-8

Veiga, R. N., de Azevedo, A. L. K., de Oliveira, J. C. & Gradia, D. F. Targeting EphA2: a promising strategy to overcome chemoresistance and drug resistance in cancer. J. Mol. Med. 102, 479–493 (2024).

pubmed: 38393661 doi: 10.1007/s00109-024-02431-x

Loges, S. et al. The combination of AXL inhibitor bemcentinib and low dose cytarabine is well tolerated and efficacious in elderly relapsed AML patients: update from the ongoing BGBC003 phase II trial (NCT02488408). Blood 136, 14–17 (2020).

doi: 10.1182/blood-2020-136566

Kubasch, A. S. et al. Efficacy and safety of bemcentinib in patients with advanced myelodysplastic neoplasms or acute myeloid leukemia failing hypomethylating agents- the EMSCO phase II BERGAMO trial. Leukemia 37, 2309–2313 (2023).

pubmed: 37735558 pmcid: 10624604 doi: 10.1038/s41375-023-02029-1

Bhalla, S. et al. Phase 1 dose escalation and expansion study of bemcentinib (BGB324), a first-in-class, selective AXL inhibitor, with docetaxel in patients with previously treated advanced NSCLC. J. Clin. Oncol. 40, 1–7 (2022).

doi: 10.1200/JCO.2022.40.16_suppl.9081

Van Tine, B. A. et al. A phase III study (APROMISS) of AL3818 (Catequentinib, Anlotinib) hydrochloride monotherapy in subjects with metastatic or advanced synovial sarcoma. J. Clin. Oncol. 39, 11505–11505 (2021).

doi: 10.1200/JCO.2021.39.15_suppl.11505

Hecht, J. R. et al. Randomized, placebo-controlled, phase III study of first-line oxaliplatin-based chemotherapy plus PTK787/ZK 222584, an oral vascular endothelial growth factor receptor inhibitor, in patients with metastatic colorectal adenocarcinoma. J. Clin. Oncol. 29, 1997–2003 (2011).

pubmed: 21464406 doi: 10.1200/JCO.2010.29.4496

Li, D. et al. Anlotinib in locally advanced or metastatic medullary thyroid carcinoma: a randomized, double-blind phase IIB trial. Clin. Cancer Res. 27, 3567–3575 (2021).

pubmed: 33832949 doi: 10.1158/1078-0432.CCR-20-2950

Ren, S. et al. First-line treatment with camrelizumab plus famitinib in advanced or metastatic NSCLC patients with PD-L1 TPS ≥1%: results from a multicenter, open-label, phase 2 trial. J. Immunother. Cancer 12 (2024).

Han, B. et al. Effect of anlotinib as a third-line or further treatment on overall survival of patients with advanced non-small cell lung cancer: the ALTER 0303 Phase 3 Randomized Clinical Trial. JAMA Oncol. 4, 1569–1575 (2018).

pubmed: 30098152 pmcid: 6248083 doi: 10.1001/jamaoncol.2018.3039

Schönherr, H. et al. Discovery of lirafugratinib (RLY-4008), a highly selective irreversible small-molecule inhibitor of FGFR2. Proc Natl Acad Sci USA 121 (2024).

Cho, B. C. et al. Amivantamab plus lazertinib in osimertinib-relapsed EGFR-mutant advanced non-small cell lung cancer: a phase 1 trial. Nat. Med. 29, 2577–2585 (2023).

pubmed: 37710001 pmcid: 10579096 doi: 10.1038/s41591-023-02554-7

Shi, Y. et al. Efficacy and safety of alflutinib (AST2818) in patients with T790M mutation-positive NSCLC: a phase IIb multicenter single-arm study. J. Clin. Oncol. 38, 9602–9602 (2020).

doi: 10.1200/JCO.2020.38.15_suppl.9602

Li, B. et al. Efficacy and safety of ASK120067 (limertinib) in patients with locally advanced or metastatic EGFR T790M-mutated non–small cell lung cancer: a multicenter, single-arm, phase IIb study. J. Clin. Oncol. 40, 9106–9106 (2022).

doi: 10.1200/JCO.2022.40.16_suppl.9106

Shi, Y. et al. Results of the phase IIa study to evaluate the efficacy and safety of rezivertinib (BPI-7711) for the first-line treatment of locally advanced or metastatic/recurrent NSCLC patients with EGFR mutation from a phase I/IIa study. BMC Med. 21 (2023).

Zhou, Q. et al. A novel third-generation EGFR tyrosine kinase inhibitor abivertinib for EGFR T790M-mutant non–small cell lung cancer: a multicenter phase I/II study. Clin. Cancer Res. 28, 1127–1135 (2022).

pubmed: 34740925 pmcid: 9365372 doi: 10.1158/1078-0432.CCR-21-2595

Shum, E. et al. A phase 1/2 study of BLU-945 in patients with common activating EGFR -mutant non–small cell lung cancer (NSCLC): SYMPHONY trial in progress. J. Clin. Oncol. 40, 9156–9156 (2022).

doi: 10.1200/JCO.2022.40.16_suppl.TPS9156

Shi, Y. et al. Efficacy and safety of rezivertinib (BPI-7711) in patients with locally advanced or metastatic/recurrent EGFR T790M-mutated NSCLC: a phase 2b study. J. Thorac. Oncol. 17, 1306–1317 (2022).

pubmed: 36049654 doi: 10.1016/j.jtho.2022.08.015

Wang, M. et al. Sunvozertinib for patients in China with platinum-pretreated locally advanced or metastatic non-small-cell lung cancer and EGFR exon 20 insertion mutation (WU-KONG6): single-arm, open-label, multicentre, phase 2 trial. Lancet Respir. Med. 12, 217–224 (2024).

pubmed: 38101437 doi: 10.1016/S2213-2600(23)00379-X

Cho, B. C. et al. Lazertinib versus gefitinib as first-line treatment in patients with EGFR-mutated advanced non–small-cell lung cancer: results from LASER301. J. Clin. Oncol. 41, 4208–4217 (2023).

pubmed: 37379502 doi: 10.1200/JCO.23.00515

Ma, F. et al. Pyrotinib versus placebo in combination with trastuzumab and docetaxel as first line treatment in patients with HER2 positive metastatic breast cancer (PHILA): randomised, double blind, multicentre, phase 3 trial. BMJ 383 (2023).

Drilon, A. E. et al. The next-generation RET inhibitor TPX-0046 is active in drug-resistant and naïve RET-driven cancer models. J. Clin. Oncol. 38, 3616–3616 (2020).

doi: 10.1200/JCO.2020.38.15_suppl.3616

Fujino, T. et al. Foretinib can overcome common on-target resistance mutations after capmatinib/tepotinib treatment in NSCLCs with MET exon 14 skipping mutation. J. Hematol. Oncol. 15, 1–14 (2022).

Xu, J. Current treatments and future potential of surufatinib in neuroendocrine tumors (NETs). Ther. Adv. Med. Oncol. 13, 1–14 (2021).

Miyazaki, I. et al. Vepafestinib is a pharmacologically advanced RET-selective inhibitor with high CNS penetration and inhibitory activity against RET solvent front mutations. Nat. Cancer 4, 1345–1361 (2023).

pubmed: 37743366 pmcid: 10518257 doi: 10.1038/s43018-023-00630-y

Lei, T. et al. Anlotinib combined with osimertinib reverses acquired osimertinib resistance in NSCLC by targeting the c-MET/MYC/AXL axis. Pharmacol. Res. 188 (2023).

Xie, L. et al. Apatinib for advanced osteosarcoma after failure of standard multimodal therapy: an open-label phase II clinical trial. Oncologist 24, 542–550 (2019).

doi: 10.1634/theoncologist.2018-0542

du Bois, A. et al. Standard first-line chemotherapy with or without nintedanib for advanced ovarian cancer (AGO-OVAR 12): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol. 17, 78–89 (2016).

pubmed: 26590673 doi: 10.1016/S1470-2045(15)00366-6

Shi, Y. et al. Safety and activity of WX-0593 (Iruplinalkib) in patients with ALK- or ROS1-rearranged advanced non-small cell lung cancer: a phase 1 dose-escalation and dose-expansion trial. Signal Transduct. Target. Ther. 7 (2022).

Parate, S., Kumar, V., Hong, J. C. & Lee, K. W. Putative dual inhibitors of mTOR and RET kinase from natural products: Pharmacophore-based hierarchical virtual screening. J. Mol. Liq. 350 (2022).

Taniguchi, H. et al. Pan-HER inhibitors overcome lorlatinib resistance caused by NRG1/HER3 activation in ALK-rearranged lung cancer. Cancer Sci. 114, 164–173 (2023).

pubmed: 36086904 doi: 10.1111/cas.15579

Wu, Y.-L. et al. Tepotinib plus gefitinib in patients with EGFR-mutant non-small-cell lung cancer with MET overexpression or MET amplification and acquired resistance to previous EGFR inhibitor (INSIGHT study): an open-label, phase 1b/2, multicentre, randomised trial. Lancet Respir. Med. 8, 1132–1143 (2020).

pubmed: 32479794 doi: 10.1016/S2213-2600(20)30154-5

Motzer, R. J. et al. Dovitinib versus sorafenib for third-line targeted treatment of patients with metastatic renal cell carcinoma: an open-label, randomised phase 3 trial. Lancet Oncol. 15, 286–296 (2014).

pubmed: 24556040 pmcid: 5719485 doi: 10.1016/S1470-2045(14)70030-0

Takumi, Y. et al. MET kinase inhibitor reverses resistance to entrectinib induced by hepatocyte growth factor in tumors with NTRK1 or ROS1 rearrangements. Cancer Med. 12, 5809–5820 (2023).

pubmed: 36416133 doi: 10.1002/cam4.5342

Lu, S. et al. Efficacy and safety of befotertinib (D-0316) in patients With EGFR T790M-mutated NSCLC that had progressed after prior EGFR tyrosine kinase inhibitor therapy: a phase 2, multicenter, single-arm, open-label study. J. Thorac. Oncol. 17, 1192–1204 (2022).

pubmed: 35724798 doi: 10.1016/j.jtho.2022.06.002

Pottier, C. et al. Tyrosine kinase inhibitors in cancer: breakthrough and challenges of targeted therapy. Cancers 12, (2020).

Xie, L. et al. Apatinib for advanced osteosarcoma after failure of standard multimodal therapy: an open label phase 2 clinical trial. J. Clin. Oncol. 36, 11520–11520 (2018).

doi: 10.1200/JCO.2018.36.15_suppl.11520

Blay, J.-Y. et al. Ripretinib in patients with advanced gastrointestinal stromal tumours (INVICTUS): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 21, 923–934 (2020).

pubmed: 32511981 pmcid: 8383051 doi: 10.1016/S1470-2045(20)30168-6

Bauer, S. et al. Ripretinib versus sunitinib in patients with advanced gastrointestinal stromal tumor after treatment with imatinib (INTRIGUE): a randomized, open-label, phase III trial. J. Clin. Oncol. 40, 3918–3928 (2022).

pubmed: 35947817 pmcid: 9746771 doi: 10.1200/JCO.22.00294

Xu, J. et al. Surufatinib in advanced pancreatic neuroendocrine tumours (SANET-p): a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 21, 1489–1499 (2020).

pubmed: 32966810 doi: 10.1016/S1470-2045(20)30493-9

Borghaei, H. et al. SAPPHIRE: phase III study of sitravatinib plus nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. Ann. Oncol. 35, 66–76 (2024).

pubmed: 37866811 doi: 10.1016/j.annonc.2023.10.004

Chen, X. et al. First-line camrelizumab (a PD-1 inhibitor) plus apatinib (an VEGFR-2 inhibitor) and chemotherapy for advanced gastric cancer (SPACE): a phase 1 study. Signal Transduct. Target. Ther. 9 (2024).

Chen, L. et al. Famitinib with camrelizumab and nab-paclitaxel for advanced immunomodulatory triple-negative breast cancer (FUTURE-C-Plus): an open-label, single-arm, phase II trial. Clin. Cancer Res. 28, 2807–2817 (2022).

pubmed: 35247906 pmcid: 9365373 doi: 10.1158/1078-0432.CCR-21-4313

Yau, T. C. C. et al. A Phase I/II multicenter study of single-agent foretinib as first-line therapy in patients with advanced hepatocellular carcinoma. Clin. Cancer Res. 23, 2405–2413 (2017).

pubmed: 27821605 doi: 10.1158/1078-0432.CCR-16-1789

Nader-Marta, G. et al. Efficacy of tyrosine kinase inhibitors for the treatment of patients with HER2-positive breast cancer with brain metastases: a systematic review and meta-analysis. ESMO Open 7 (2022).

Wu, J. et al. Neoadjuvant pyrotinib, trastuzumab, and docetaxel for HER2-positive breast cancer (PHEDRA): a double-blind, randomized phase 3 trial. BMC Med. 20 (2022).

Xu, B. et al. Pyrotinib plus capecitabine versus lapatinib plus capecitabine for the treatment of HER2-positive metastatic breast cancer (PHOEBE): a multicentre, open-label, randomised, controlled, phase 3 trial. Lancet Oncol. 22, 351–360 (2021).

pubmed: 33581774 doi: 10.1016/S1470-2045(20)30702-6

Hartmaier, R. J. et al. Osimertinib + savolitinib to overcome acquired MET-mediated resistance in epidermal growth factor receptor-mutated, MET-amplified non-small cell lung cancer: TATTON. Cancer Discov. 13, 98–113 (2023).

pubmed: 36264123 doi: 10.1158/2159-8290.CD-22-0586

Passaro, A. et al. Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: primary results from the phase III MARIPOSA-2 study. Ann. Oncol. 35, 77–90 (2024).

pubmed: 37879444 doi: 10.1016/j.annonc.2023.10.117

Zhou, Q. et al. Safety and efficacy of epitinib for EGFR-mutant non-small cell lung cancer with brain metastases: open-label multicentre dose-expansion phase Ib study. Clin. Lung Cancer 23, 353–361 (2022).

doi: 10.1016/j.cllc.2022.03.014

Shi, Y. et al. Furmonertinib (AST2818) versus gefitinib as first-line therapy for Chinese patients with locally advanced or metastatic EGFR mutation-positive non-small-cell lung cancer (FURLONG): a multicentre, double-blind, randomised phase 3 study. Lancet Respir. Med. 10, 1019–1028 (2022).

pubmed: 35662408 doi: 10.1016/S2213-2600(22)00168-0

Choi, Y. W. et al. Differential efficacy of tyrosine kinase inhibitors (TKIs) according to the types of EGFR mutations and agents in non-small cell lung cancer (NSCLC): a real-world study. J. Clin. Oncol. 41, 21040–21040 (2023).

doi: 10.1200/JCO.2023.41.16_suppl.e21040

Choueiri, T. K. et al. Cabozantinib versus sunitinib as initial targeted therapy for patients with metastatic renal cell carcinoma of poor or intermediate risk: the alliance A031203 CABOSUN trial. J. Clin. Oncol. 35, 591–597 (2017).

pubmed: 28199818 doi: 10.1200/JCO.2016.70.7398

Fachi, M. M. et al. Comparative efficacy and safety of tyrosine kinase inhibitors for chronic myeloid leukaemia: a systematic review and network meta-analysis. Eur. J. Cancer 104, 9–20 (2018).

pubmed: 30296736 doi: 10.1016/j.ejca.2018.08.016

Zhang, X. et al. Receptor specificity of the fibroblast growth factor family. The complete mammalian FGF family. J. Biol. Chem. 281, 15694–15700 (2006).

pubmed: 16597617 doi: 10.1074/jbc.M601252200

Ward, C. W. & Lawrence, M. C. Ligand-induced activation of the insulin receptor: a multi-step process involving structural changes in both the ligand and the receptor. Bioessays 31, 422–434 (2009).

pubmed: 19274663 doi: 10.1002/bies.200800210

Olsson, A.-K., Dimberg, A., Kreuger, J. & Claesson-Welsh, L. VEGF receptor signalling - in control of vascular function. Nat. Rev. Mol. Cell Biol. 7, 359–371 (2006).

pubmed: 16633338 doi: 10.1038/nrm1911

Graveel, C. R., Tolbert, D. & Vande Woude, G. F. MET: a critical player in tumorigenesis and therapeutic target. Cold Spring Harb. Perspect. Biol. 5, (2013).

Hubbard, S. R. & Gnanasambandan, K. Structure and activation of MuSK, a receptor tyrosine kinase central to neuromuscular junction formation. Biochim. Biophys. Acta 1834, 2166–2169 (2013).

pubmed: 23467009 pmcid: 3923368 doi: 10.1016/j.bbapap.2013.02.034

De Munck, S. et al. Structural basis of cytokine-mediated activation of ALK family receptors. Nature 600, 143–147 (2021).

pubmed: 34646012 pmcid: 9343967 doi: 10.1038/s41586-021-03959-5

Hallberg, B. & Palmer, R. H. Mechanistic insight into ALK receptor tyrosine kinase in human cancer biology. Nat. Rev. Cancer 13, 685–700 (2013).

pubmed: 24060861 doi: 10.1038/nrc3580

Menck, K., Heinrichs, S., Baden, C. & Bleckmann, A. The WNT/ROR pathway in cancer: from signaling to therapeutic intervention. Cells 10 (2021).

van Amerongen, R., Mikels, A. & Nusse, R. Alternative wnt signaling is initiated by distinct receptors. Sci. Signal 1, re9 (2008).

pubmed: 18765832

Naitoh, A. et al. Study of lymphoscintigraphy with 99mTc rhenium colloid for diagnosis of lymphedema. Rinsho Hoshasen 28, 663–668 (1983).

pubmed: 6620610

Fu, Y., Chen, Y., Huang, J., Cai, Z. & Wang, Y. RYK, a receptor of noncanonical Wnt ligand Wnt5a, is positively correlated with gastric cancer tumorigenesis and potential of liver metastasis. Am. J. Physiol. Gastrointest. Liver Physiol. 318, 352–360 (2020).

doi: 10.1152/ajpgi.00228.2019

Skaper, S. D. The neurotrophin family of neurotrophic factors: an overview. In: Skaper, S. (eds) Neurotrophic Factors. Methods in Molecular Biology (ed. Skaper, S.) vol. 846 1–12 (Humana Press, 2012).

Caberoy, N. B., Zhou, Y. & Li, W. Tubby and tubby-like protein 1 are new MerTK ligands for phagocytosis. EMBO J. 29, 3898–3910 (2010).

pubmed: 20978472 pmcid: 3020645 doi: 10.1038/emboj.2010.265

Lemke, G. Biology of the TAM receptors. Cold Spring Harb. Perspect. Biol. 5, 9076–9076 (2013).

doi: 10.1101/cshperspect.a009076

Maisonpierre, P. C. et al. Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science 277, 55–60 (1997).

pubmed: 9204896 doi: 10.1126/science.277.5322.55

Labrador, J. P. et al. The collagen receptor DDR2 regulates proliferation and its elimination leads to dwarfism. EMBO Rep. 2, 446–452 (2001).

pubmed: 11375938 pmcid: 1083888 doi: 10.1093/embo-reports/kve094

Vogel, W. F., Aszódi, A., Alves, F. & Pawson, T. Discoidin domain receptor 1 tyrosine kinase has an essential role in mammary gland development. Mol. Cell Biol. 21, 2906–2917 (2001).

pubmed: 11283268 pmcid: 86919 doi: 10.1128/MCB.21.8.2906-2917.2001

Arrieta, O. et al. Updated frequency of EGFR and KRAS mutations in non small-cell lung cancer in Latin America: the Latin-American Consortium for the Investigation of Lung Cancer (CLICaP). J. Thorac. Oncol. 10, 838–843 (2015).

pubmed: 25634006 doi: 10.1097/JTO.0000000000000481

Banno, E. et al. Sensitivities to various epidermal growth factor receptor‐tyrosine kinase inhibitors of uncommon epidermal growth factor receptor mutations L861Q and S768I: What is the optimal epidermal growth factor receptor‐tyrosine kinase inhibitor? Cancer Sci. 107, 1134–1140 (2016).

pubmed: 27240419 pmcid: 4982590 doi: 10.1111/cas.12980

André, F. et al. AACR project GENIE: powering precision medicine through an International Consortium. Cancer Discov. 7, 818–831 (2017).

doi: 10.1158/2159-8290.CD-17-0151

Suda, K., Onozato, R., Yatabe, Y. & Mitsudomi, T. EGFR T790M mutation: a double role in lung cancer cell survival? J. Thorac. Oncol. 4, 1–4 (2009).

pubmed: 19096299 doi: 10.1097/JTO.0b013e3181913c9f

Gessi, M. et al. FGFR1 mutations in rosette-forming glioneuronal tumors of the fourth ventricle. J. Neuropathol. Exp. Neurol. 73, 580–584 (2014).

pubmed: 24806303 doi: 10.1097/NEN.0000000000000080

Jones, D. T. W. et al. Recurrent somatic alterations of FGFR1 and NTRK2 in pilocytic astrocytoma. Nat. Genet. 45, 927–932 (2013).

pubmed: 23817572 pmcid: 3951336 doi: 10.1038/ng.2682

Dulak, A. M. et al. Exome and whole-genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity. Nat. Genet. 45, 478–486 (2013).

pubmed: 23525077 pmcid: 3678719 doi: 10.1038/ng.2591

Li, J. J. et al. FGFR genes mutation is an independent prognostic factor and associated with lymph node metastasis in squamous non-small cell lung cancer. Cancer Biol. Ther. 19, 1108–1116 (2018).

pubmed: 30403900 pmcid: 6301818 doi: 10.1080/15384047.2018.1480294

Nakamura, I. T. et al. Comprehensive functional evaluation of variants of fibroblast growth factor receptor genes in cancer. NPJ Precis. Oncol. 5 (2021).

Dienstmann, R. et al. Genomic aberrations in the FGFR pathway: opportunities for targeted therapies in solid tumors. Ann. Oncol. 25, 552–563 (2014).

pubmed: 24265351 doi: 10.1093/annonc/mdt419

Ascione, C. M. et al. Role of FGFR3 in bladder cancer: treatment landscape and future challenges. Cancer Treat. Rev. 115 (2023).

Tomlinson, D. C., Hurst, C. D. & Knowles, M. A. Knockdown by shRNA identifies S249C mutant FGFR3 as a potential therapeutic target in bladder cancer. Oncogene 26, 5889–5899 (2007).

pubmed: 17384684 pmcid: 2443272 doi: 10.1038/sj.onc.1210399

Aubertin, J., Tourpin, S., Janot, F., Ahomadegbe, J. & Radvanyi, F. Analysis of fibroblast growth factor receptor 3 G697C mutation in oral squamous cell carcinomas. Int. J. Cancer 120, 2058–2059 (2007).

pubmed: 17044022 doi: 10.1002/ijc.22285

Futami, T. et al. Identification of a novel oncogenic mutation of FGFR4 in gastric cancer. Sci. Rep. 9, 1–9 (2019).

doi: 10.1038/s41598-019-51217-6

Chew, N. J. et al. Evaluation of FGFR targeting in breast cancer through interrogation of patient-derived models. Breast Cancer Res. 23 (2021).

Boucher, J., Kleinridders, A. & Kahn, C. R. Insulin receptor signaling in normal and insulin-resistant states. Cold Spring Harb. Perspect. Biol. 6 (2014).

Cuenca, D. et al. A novel nonsense mutation in the insulin receptor gene in a patient with HAIR-AN syndrome and endometrial cancer. Mol. Genet. Metab. Rep. 35 (2023).

Esposito, D. L. et al. Novel insulin receptor substrate 1 and 2 variants in breast and colorectal cancer. Oncol. Rep. 30, 1553–1560 (2013).

pubmed: 23877285 pmcid: 3810354 doi: 10.3892/or.2013.2626

Khurshid, S. et al. Splice-switching of the insulin receptor pre-mRNA alleviates tumorigenic hallmarks in rhabdomyosarcoma. NPJ Precis. Oncol. 6 (2022).

Vella, V. & Malaguarnera, R. The emerging role of insulin receptor isoforms in thyroid cancer: clinical implications and new perspectives. Int. J. Mol. Sci. 19 (2018).

Frasca, F. et al. The role of insulin receptors and IGF-I receptors in cancer and other diseases. Arch. Physiol. Biochem. 114, 23–37 (2008).

pubmed: 18465356 doi: 10.1080/13813450801969715

Qian, H. et al. The clinical significance of platelet-derived growth factors (PDGFs) and their receptors (PDGFRs) in gastric cancer: a systematic review and meta-analysis. Crit. Rev. Oncol. Hematol. 127, 15–28 (2018).

pubmed: 29891108 doi: 10.1016/j.critrevonc.2018.05.004

Randomized trial of crenolanib in subjects with D842V mutated GIST. https://clinicaltrials.gov/study/NCT02847429 .

Study of crenolanib for the treatment of patients with advanced GIST with the D842-related mutations and deletions in the PDGFRA gene. https://clinicaltrials.gov/study/NCT01243346 .

Corless, C. L. et al. PDGFRA mutations in gastrointestinal stromal tumors: frequency, spectrum and in vitro sensitivity to imatinib. J. Clin. Oncol. 23, 5357–5364 (2005).

pubmed: 15928335 doi: 10.1200/JCO.2005.14.068

Joensuu, H. et al. Effect of KIT and PDGFRA mutations on survival in patients with gastrointestinal stromal tumors treated with adjuvant imatinib. JAMA Oncol. 3, 602–609 (2017).

pubmed: 28334365 pmcid: 5470395 doi: 10.1001/jamaoncol.2016.5751

Debiec-Rychter, M. et al. Use of c-KIT/PDGFRA mutational analysis to predict the clinical response to imatinib in patients with advanced gastrointestinal stromal tumours entered on phase I and II studies of the EORTC Soft Tissue and Bone Sarcoma Group. Eur. J. Cancer 40, 689–695 (2004).

pubmed: 15010069 doi: 10.1016/j.ejca.2003.11.025

Cassier, P. A. et al. Outcome of patients with platelet-derived growth factor receptor alpha-mutated gastrointestinal stromal tumors in the tyrosine kinase inhibitor era. Clin. Cancer Res. 18, 4458–4464 (2012).

pubmed: 22718859 doi: 10.1158/1078-0432.CCR-11-3025

Yoo, C. et al. Efficacy of imatinib in patients with platelet-derived growth factor receptor alpha-mutated gastrointestinal stromal tumors. Cancer Res. Treat. 48, 546–552 (2016).

pubmed: 26130666 doi: 10.4143/crt.2015.015

Heinrich, M. C. et al. PDGFRA activating mutations in gastrointestinal stromal tumors. Science 299, 708–710 (2003).

pubmed: 12522257 doi: 10.1126/science.1079666

Klempner, S. J. et al. Carving out another slice of the pie: exceptional response to single agent imatinib in an Asian female never-smoker with advanced NSCLC with a de-novo PDGFR-α N848 K mutation. Lung Cancer 124, 86–89 (2018).

pubmed: 30268485 doi: 10.1016/j.lungcan.2018.07.043

Yi, E. S., Strong, C. R., Piao, Z., Perucho, M. & Weidner, N. Epithelioid Gastrointestinal Stromal Tumor With PDGFRA Activating Mutation and Immunoreactivity. Appl Immunohistochem. Mol. Morphol. 13, 157–161 (2005).

pubmed: 15894928 doi: 10.1097/01.pai.0000156607.04726.9a

Velghe, A. I. et al. PDGFRA alterations in cancer: characterization of a gain-of-function V536E transmembrane mutant as well as loss-of-function and passenger mutations. Oncogene 33, 2568–2576 (2014).

pubmed: 23752188 doi: 10.1038/onc.2013.218

Ozawa, T. et al. PDGFRA gene rearrangements are frequent genetic events in PDGFRA-amplified glioblastomas. Genes Dev. 24, 2205–2218 (2010).

pubmed: 20889717 pmcid: 2947772 doi: 10.1101/gad.1972310

Dai, J. et al. Large-scale analysis of PDGFRA mutations in melanomas and evaluation of their sensitivity to tyrosine kinase inhibitors imatinib and crenolanib. Clin. Cancer Res. 19, 6935–6942 (2013).

pubmed: 24132921 doi: 10.1158/1078-0432.CCR-13-1266

Cheung, Y. H. et al. A recurrent PDGFRB mutation causes familial infantile myofibromatosis. Am. J. Hum. Genet. 92, 996–1000 (2013).

pubmed: 23731537 pmcid: 3675240 doi: 10.1016/j.ajhg.2013.04.026

Arts, F. A. et al. PDGFRB mutants found in patients with familial infantile myofibromatosis or overgrowth syndrome are oncogenic and sensitive to imatinib. Oncogene 35, 3239–3248 (2016).

pubmed: 26455322 doi: 10.1038/onc.2015.383

Debiec-Rychter, M. et al. KIT mutations and dose selection for imatinib in patients with advanced gastrointestinal stromal tumours. Eur. J. Cancer 42, 1093–1103 (2006).

pubmed: 16624552 doi: 10.1016/j.ejca.2006.01.030

Wozniak, A. et al. Tumor genotype is an independent prognostic factor in primary gastrointestinal stromal tumors of gastric origin: a European multicenter analysis based on ConticaGIST. Clin. Cancer Res. 20, 6105–6116 (2014).

pubmed: 25294914 doi: 10.1158/1078-0432.CCR-14-1677

Wozniak, A. et al. Prognostic value of KIT/PDGFRA mutations in gastrointestinal stromal tumours (GIST): Polish Clinical GIST Registry experience. Ann. Oncol. 23, 353–360 (2012).

pubmed: 21527588 doi: 10.1093/annonc/mdr127

Heinrich, M. C. et al. Correlation of kinase genotype and clinical outcome in the North American Intergroup Phase III trial of imatinib mesylate for treatment of advanced gastrointestinal stromal tumor: CALGB 150105 Study by Cancer and Leukemia Group B and Southwest Oncology Group. J. Clin. Oncol. 26, 5360–5367 (2008).

pubmed: 18955451 pmcid: 2651078 doi: 10.1200/JCO.2008.17.4284

Szucs, Z. et al. Molecular subtypes of gastrointestinal stromal tumors and their prognostic and therapeutic implications. Future Oncol. 13, 93–107 (2017).

pubmed: 27600498 doi: 10.2217/fon-2016-0192

Lennartsson, J., Jelacic, T., Linnekin, D. & Shivakrupa, R. Normal and oncogenic forms of the receptor tyrosine kinase Kit. Stem Cells 23, 16–43 (2005).

pubmed: 15625120 doi: 10.1634/stemcells.2004-0117

Carvajal, R. D. et al. Phase II study of nilotinib in melanoma harboring KIT alterations following progression to prior KIT inhibition. Clin. Cancer Res. 21, 2289–2296 (2015).

pubmed: 25695690 pmcid: 5013827 doi: 10.1158/1078-0432.CCR-14-1630

Pham, D. D. M., Guhan, S. & Tsao, H. KIT and Melanoma: biological Insights and Clinical Implications. Yonsei Med. J. 61, 562–571 (2020).

pubmed: 32608199 doi: 10.3349/ymj.2020.61.7.562

Funkhouser, A. T. et al. KIT Mutations correlate with higher galectin levels and brain metastasis in breast and non-small cell lung cancer. Cancers 14 (2022).

Arock, M. et al. KIT mutation analysis in mast cell neoplasms: recommendations of the European Competence Network on Mastocytosis. Leukemia 29, 1223–1232 (2015).

pubmed: 25650093 pmcid: 4522520 doi: 10.1038/leu.2015.24

Naumann, N. et al. Adverse prognostic impact of the KIT D816V transcriptional activity in advanced systemic mastocytosis. Int. J. Mol. Sci. 22 (2021).

Abdellateif, M., Bayoumi, A. & Mohammed, M. c-Kit receptors as a therapeutic target in cancer: current insights. Onco Targets Ther. 16, 785–799 (2023).

pubmed: 37790582 pmcid: 10544070 doi: 10.2147/OTT.S404648

McIntyre, A. et al. Amplification and overexpression of the KIT gene is associated with progression in the seminoma subtype of testicular germ cell tumors of adolescents and adults. Cancer Res. 65, 8085–8089 (2005).

pubmed: 16166280 doi: 10.1158/0008-5472.CAN-05-0471

Nakai, Y. et al. KIT (c-kit oncogene product) pathway is constitutively activated in human testicular germ cell tumors. Biochem. Biophys. Res. Commun. 337, 289–296 (2005).

pubmed: 16188233 doi: 10.1016/j.bbrc.2005.09.042

Sletta, K. Y., Castells, O. & Gjertsen, B. T. Colony stimulating factor 1 receptor in acute myeloid leukemia. Front. Oncol. 11 (2021).

Ridge, S. A., Worwood, M., Oscier, D., Jacobs, A. & Padua, R. A. FMS mutations in myelodysplastic, leukemic, and normal subjects. Proc. Natl Acad. Sci. USA 87, 1377–1380 (1990).

pubmed: 2406720 pmcid: 53478 doi: 10.1073/pnas.87.4.1377

Soares, M. J. et al. CSF1R copy number changes, point mutations, and RNA and protein overexpression in renal cell carcinomas. Mod. Pathol. 22, 744–752 (2009).

pubmed: 19377443 doi: 10.1038/modpathol.2009.43

Kiyoi, H., Kawashima, N. & Ishikawa, Y. FLT3 mutations in acute myeloid leukemia: therapeutic paradigm beyond inhibitor development. Cancer Sci. 111, 312–322 (2020).

pubmed: 31821677 doi: 10.1111/cas.14274

Simons, M., Gordon, E. & Claesson-Welsh, L. Mechanisms and regulation of endothelial VEGF receptor signalling. Nat. Rev. Mol. Cell Biol. 17, 611–625 (2016).

pubmed: 27461391 doi: 10.1038/nrm.2016.87

Mabeta, P. & Steenkamp, V. The VEGF/VEGFR axis revisited: implications for cancer therapy. Int. J. Mol. Sci. 23 (2022).

Loaiza-Bonilla, A. et al. KDR mutation as a novel predictive biomarker of exceptional response to regorafenib in metastatic colorectal cancer. Cureus 8 (2016).

Kumar, R. D. & Bose, R. Analysis of somatic mutations across the kinome reveals loss-of-function mutations in multiple cancer types. Sci. Rep. 7 (2017).

Antonescu, C. R. et al. KDR activating mutations in human angiosarcomas are sensitive to specific kinase inhibitors. Cancer Res. 69, 7175–7179 (2009).

pubmed: 19723655 pmcid: 2763376 doi: 10.1158/0008-5472.CAN-09-2068

Wei, L. et al. Dramatic response of CTNNB1 and VEGFR-2 mutant temporal bone squamous cell carcinoma to bevacizumab in combination with pemetrexed. Oncotarget 8, 57898–57904 (2017).

pubmed: 28915721 pmcid: 5593693 doi: 10.18632/oncotarget.19649

Ravi, V. et al. Antitumor response of VEGFR2- and VEGFR3-amplified angiosarcoma to pazopanib. J. Natl Compr. Cancer Netw. 14, 499–502 (2016).

doi: 10.6004/jnccn.2016.0058

Peghini, P. L. et al. Overexpression of epidermal growth factor and hepatocyte growth factor receptors in a proportion of gastrinomas correlates with aggressive growth and lower curability. Clin. Cancer Res. 8, 2273–2285 (2002).

pubmed: 12114431

Matsumoto, K., Umitsu, M., De Silva, D. M., Roy, A. & Bottaro, D. P. Hepatocyte growth factor/MET in cancer progression and biomarker discovery. Cancer Sci. 108, 296–307 (2017).

pubmed: 28064454 pmcid: 5378267 doi: 10.1111/cas.13156

Yano, S. et al. Hepatocyte growth factor expression in EGFR mutant lung cancer with intrinsic and acquired resistance to tyrosine kinase inhibitors in a Japanese cohort. J. Thorac. Oncol. 6, 2011–2017 (2011).

pubmed: 22052230 doi: 10.1097/JTO.0b013e31823ab0dd

De Silva, D. M. et al. Targeting the hepatocyte growth factor/Met pathway in cancer. Biochem. Soc. Trans. 45, 855–870 (2017).

pubmed: 28673936 doi: 10.1042/BST20160132

Stone, A. EGFR and c-met inhibitors are effective in reducing tumorigenicity in cancer. J. Carcinog. Mutagen 5, 1–9 (2014).

doi: 10.4172/2157-2518.1000173

Xu, J., Wang, J. & Zhang, S. Mechanisms of resistance to irreversible epidermal growth factor receptor tyrosine kinase inhibitors and therapeutic strategies in non-small cell lung cancer. Oncotarget 8, 90557–90578 (2017).

pubmed: 29163853 pmcid: 5685774 doi: 10.18632/oncotarget.21164

Oh, S. et al. Precision targeting of autoantigen-specific B cells in muscle-specific tyrosine kinase myasthenia gravis with chimeric autoantibody receptor T cells. Nat. Biotechnol. 41, 1229–1238 (2023).

pubmed: 36658341 pmcid: 10354218 doi: 10.1038/s41587-022-01637-z

Gainor, J. F. et al. Patterns of metastatic spread and mechanisms of resistance to crizotinib in ROS1-positive non-small-cell lung cancer. JCO Precis. Oncol. 1, 1–13 (2017).

doi: 10.1200/PO.17.00063

Drilon, A. et al. A novel crizotinib-resistant solvent-front mutation responsive to cabozantinib therapy in a patient with ROS1-rearranged lung cancer. Clin. Cancer Res. 22, 2351–2358 (2016).

pubmed: 26673800 doi: 10.1158/1078-0432.CCR-15-2013

Mahato, A. K. & Sidorova, Y. A. RET receptor tyrosine kinase: role in neurodegeneration, obesity, and cancer. Int. J. Mol. Sci. 21 (2020).

Bardelli, A. et al. Mutational analysis of the tyrosine kinome in colorectal cancers. Science 300, 949–949 (2003).

pubmed: 12738854 doi: 10.1126/science.1082596

Bonkowsky, J. L., Yoshikawa, S., O’Keefe, D. D., Scully, A. L. & Thomas, J. B. Axon routing across the midline controlled by the Drosophila Derailed receptor. Nature 402, 540–544 (1999).

pubmed: 10591215 doi: 10.1038/990122

Sasaki, T. et al. A novel ALK secondary mutation and EGFR signaling cause resistance to ALK kinase inhibitors. Cancer Res. 71, 6051–6060 (2011).

pubmed: 21791641 pmcid: 3278914 doi: 10.1158/0008-5472.CAN-11-1340

Joshi, S. K. et al. The FLT3N701K mutation causes clinical AML resistance to gilteritinib and triggers TKI sensitivity switch to quizartinib. Am. J. Hematol. 98, 364–368 (2023).

doi: 10.1002/ajh.27096

Freire, T. S., Caracelli, I., Zukerman-Schpector, J. & Friedman, R. Resistance to a tyrosine kinase inhibitor mediated by changes to the conformation space of the kinase. Phys. Chem. Chem. Phys. 25, 6175–6183 (2023).

pubmed: 36752538 doi: 10.1039/D2CP05549J

Napolitano, A. & Vincenzi, B. Secondary KIT mutations: the GIST of drug resistance and sensitivity. Br. J. Cancer 120, 577–578 (2019).

pubmed: 30792534 pmcid: 6461933 doi: 10.1038/s41416-019-0388-7

Gramza, A. W., Corless, C. L. & Heinrich, M. C. Resistance to tyrosine kinase inhibitors in gastrointestinal stromal tumors. Clin. Cancer Res. 15, 7510–7518 (2009).

pubmed: 20008851 doi: 10.1158/1078-0432.CCR-09-0190

Chen, Y. et al. SPK1/S1P axis confers gastrointestinal stromal tumors (GISTs) resistance of imatinib. Gastric Cancer 26, 26–43 (2023).

pubmed: 35999321 doi: 10.1007/s10120-022-01332-7

Jiang, L. et al. Low frequency KRAS mutations in colorectal cancer patients and the presence of multiple mutations in oncogenic drivers in non-small cell lung cancer patients. Cancer Genet. 206, 330–339 (2013).

pubmed: 24200637 doi: 10.1016/j.cancergen.2013.09.004

Xie, Y.-H., Chen, Y.-X. & Fang, J.-Y. Comprehensive review of targeted therapy for colorectal cancer. Signal Transduct. Target. Ther. 5 (2020).

Lim, M. et al. EGFR/ERBB2 Amplifications and Alterations Associated With Resistance to Lenvatinib inHepatocellular Carcinoma. Gastroenterology 164, 1006–1008 (2023).

Desbois-Mouthon, C. et al. Insulin-like growth factor-1 receptor inhibition induces a resistance mechanism via the epidermal growth factor receptor/HER3/AKT signaling pathway: rational basis for cotargeting insulin-like growth factor-1 receptor and epidermal growth factor receptor in hepatocellular carcinoma. Clin. Cancer Res. 15, 5445–5456 (2009).

pubmed: 19706799 doi: 10.1158/1078-0432.CCR-08-2980

Gu, L., Jin, X., Liang, H., Yang, C. & Zhang, Y. Upregulation of CSNK1A1 induced by ITGB5 confers to hepatocellular carcinoma resistance to sorafenib in vivo by disrupting the EPS15/EGFR complex. Pharmacol. Res. 192 (2023).

Khan, H. Y. et al. Targeting XPO1 and PAK4 in 8505C anaplastic thyroid cancer cells: putative implications for overcoming lenvatinib therapy resistance. Int. J. Mol. Sci. 21 (2019).

Feng, H. et al. FOXK2 transcriptionally activating VEGFA induces apatinib resistance in anaplastic thyroid cancer through VEGFA/VEGFR1 pathway. Oncogene 40, 6115–6129 (2021).

pubmed: 34489549 doi: 10.1038/s41388-021-01830-5

Bertol, B. C. et al. Lenvatinib plus Anti-PD-1 combination therapy for advanced cancers: defining mechanisms of resistance in an inducible transgenic model of thyroid cancer. Thyroid 32, 153–163 (2022).

pubmed: 34641722 pmcid: 8861922 doi: 10.1089/thy.2021.0371

Patel, M. et al. Resistance to molecularly targeted therapies in melanoma. Cancers 13 (2021).

Kakadia, S. et al. Mechanisms of resistance to BRAF and MEK inhibitors and clinical update of US Food and Drug Administration-approved targeted therapy in advanced melanoma. Onco Targets Ther. 11, 7095–7107 (2018).

pubmed: 30410366 pmcid: 6200076 doi: 10.2147/OTT.S182721

Marín, A. et al. Acquired secondary HER2 mutations enhance HER2/MAPK signaling and promote resistance to HER2 kinase inhibition in breast cancer. Cancer Res. 83, 3145–3158 (2023).

pubmed: 37404061 pmcid: 10530374 doi: 10.1158/0008-5472.CAN-22-3617

Rini, B. I. & Atkins, M. B. Resistance to targeted therapy in renal-cell carcinoma. Lancet Oncol. 10, 992–1000 (2009).

pubmed: 19796751 doi: 10.1016/S1470-2045(09)70240-2

Makhov, P. et al. Resistance to systemic therapies in clear cell renal cell carcinoma: mechanisms and management strategies. Mol. Cancer Ther. 17, 1355–1364 (2018).

pubmed: 29967214 pmcid: 6034114 doi: 10.1158/1535-7163.MCT-17-1299

Jeong, S. U. et al. PD-L1 upregulation by the mTOR pathway in VEGFR-TKI-resistant metastatic clear cell renal cell carcinoma. Cancer Res. Treat. 55, 231–244 (2023).

pubmed: 35240013 doi: 10.4143/crt.2021.1526

Sweeney, P. L., Suri, Y., Basu, A., Koshkin, V. S. & Desai, A. Mechanisms of tyrosine kinase inhibitor resistance in renal cell carcinoma. Cancer Drug Resist. 6, 858–873 (2023).

pubmed: 38239394 pmcid: 10792482 doi: 10.20517/cdr.2023.89

Facchinetti, F. et al. Resistance to selective FGFR Inhibitors in FGFR-driven urothelial cancer. Cancer Discov. 13, 1998–2011 (2023).

pubmed: 37377403 pmcid: 10481128 doi: 10.1158/2159-8290.CD-22-1441

Van Cutsem, E. et al. Nintedanib for the treatment of patients with refractory metastatic colorectal cancer (LUME-Colon 1): a phase III, international, randomized, placebo-controlled study. Ann. Oncol. 29, 1955–1963 (2018).

pubmed: 30010751 pmcid: 6158765 doi: 10.1093/annonc/mdy241

Shi, Y.-K. et al. Safety and activity of alflutinib in patients with advanced EGFR T790M mutation non-small cell lung cancer who progressed after EGFR-TKI therapy. Ann. Oncol. 30, 1531–1531 (2019).

doi: 10.1093/annonc/mdz260.053

Lu, S. et al. AENEAS: a randomized phase III trial of aumolertinib versus gefitinib as first-line therapy for locally advanced or metastatic non–small-cell lung cancer with EGFR exon 19 deletion or L858R mutations. J. Clin. Oncol. 40, 3162–3171 (2022).

pubmed: 35580297 pmcid: 9509093 doi: 10.1200/JCO.21.02641

Lu, S. et al. Befotertinib (D-0316) versus icotinib as first-line therapy for patients with EGFR-mutated locally advanced or metastatic non-small-cell lung cancer: a multicentre, open-label, randomised phase 3 study. Lancet Respir. Med. 11, 905–915 (2023).

pubmed: 37244266 doi: 10.1016/S2213-2600(23)00183-2

Zhao, H. et al. Apatinib plus gefitinib as first-line treatment in advanced EGFR-mutant NSCLC: the phase III ACTIVE study (CTONG1706). J. Thorac. Oncol. 16, 1533–1546 (2021).

pubmed: 34033974 doi: 10.1016/j.jtho.2021.05.006

DeAngelo, D. J. et al. Phase 1 clinical results with tandutinib (MLN518), a novel FLT3 antagonist, in patients with acute myelogenous leukemia or high-risk myelodysplastic syndrome: safety, pharmacokinetics, and pharmacodynamics. Blood 108, 3674–3681 (2006).

pubmed: 16902153 pmcid: 1895460 doi: 10.1182/blood-2006-02-005702

Shi, Y. et al. Efficacy and safety of iruplinalkib (WX-0593) in ALK-positive crizotinib-resistant advanced non-small cell lung cancer patients: a single-arm, multicenter phase II study (INTELLECT). BMC Med. 21 (2023).

Therapeutic advances of targeting receptor tyrosine kinases in cancer.

Journal

Informations de publication

Résumé

Identifiants

Substances chimiques

Types de publication

Langues

Sous-ensembles de citation

Pagination

Informations de copyright

Références

Auteurs

Ciprian Tomuleasa (C)

Adrian-Bogdan Tigu (AB)

Raluca Munteanu (R)

Cristian-Silviu Moldovan (CS)

David Kegyes (D)

Anca Onaciu (A)

Diana Gulei (D)

Gabriel Ghiaur (G)

Hermann Einsele (H)

Carlo M Croce (CM)

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Smoking Cessation and Incident Cardiovascular Disease.

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Classifications MeSH