Molecular biomarkers of progression in non-muscle-invasive bladder cancer - beyond conventional risk stratification.
Journal
Nature reviews. Urology
ISSN: 1759-4820
Titre abrégé: Nat Rev Urol
Pays: England
ID NLM: 101500082
Informations de publication
Date de publication:
02 Aug 2024
02 Aug 2024
Historique:
accepted:
21
06
2024
medline:
3
8
2024
pubmed:
3
8
2024
entrez:
2
8
2024
Statut:
aheadofprint
Résumé
The global incidence of bladder cancer is more than half a million diagnoses each year. Bladder cancer can be categorized into non-muscle-invasive bladder cancer (NMIBC), which accounts for ~75% of diagnoses, and muscle-invasive bladder cancer (MIBC). Up to 45% of patients with NMIBC develop disease progression to MIBC, which is associated with a poor outcome, highlighting a clinical need to identify these patients. Current risk stratification has a prognostic value, but relies solely on clinicopathological parameters that might not fully capture the complexity of disease progression. Molecular research has led to identification of multiple crucial players involved in NMIBC progression. Identified biomarkers of progression are related to cell cycle, MAPK pathways, apoptosis, tumour microenvironment, chromatin stability and DNA-damage response. However, none of these biomarkers has been prospectively validated. Reported gene signatures of progression do not improve NMIBC risk stratification. Molecular subtypes of NMIBC have improved our understanding of NMIBC progression, but these subtypes are currently unsuitable for clinical implementation owing to a lack of prospective validation, limited predictive value as a result of intratumour subtype heterogeneity, technical challenges, costs and turnaround time. Future steps include the development of consensus molecular NMIBC subtypes that might improve conventional clinicopathological risk stratification. Prospective implementation studies of biomarkers and the design of biomarker-guided clinical trials are required for the integration of molecular biomarkers into clinical practice.
Identifiants
pubmed: 39095581
doi: 10.1038/s41585-024-00914-7
pii: 10.1038/s41585-024-00914-7
doi:
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024. Springer Nature Limited.
Références
Bray, F. et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 74, 229–263 (2024).
pubmed: 38572751
doi: 10.3322/caac.21834
Saginala, K. et al. Epidemiology of bladder cancer. Med. Sci. 8, 15 (2020).
Sylvester, R. J. et al. Predicting recurrence and progression in individual patients with stage Ta T1 bladder cancer using EORTC risk tables: a combined analysis of 2596 patients from seven EORTC trials. Eur. Urol. 49, 466–475; discussion 475–477 (2006).
pubmed: 16442208
doi: 10.1016/j.eururo.2005.12.031
Babjuk, M. et al. European Association of Urology guidelines on non-muscle-invasive bladder cancer (Ta, T1, and carcinoma in situ). Eur. Urol. 81, 75–94 (2022).
pubmed: 34511303
doi: 10.1016/j.eururo.2021.08.010
Ge, P. et al. Oncological outcome of primary and secondary muscle-invasive bladder cancer: a systematic review and meta-analysis. Sci. Rep. 8, 7543 (2018).
pubmed: 29765120
pmcid: 5954122
doi: 10.1038/s41598-018-26002-6
D’Andrea, D. et al. The impact of primary versus secondary muscle-invasive bladder cancer at diagnosis on the response to neoadjuvant chemotherapy. Eur. Urol. Open. Sci. 41, 74–80 (2022).
pubmed: 35813257
pmcid: 9257642
doi: 10.1016/j.euros.2022.05.001
Pones, M. et al. Differential prognosis and response of denovo vs. secondary muscle-invasive bladder cancer: an updated systematic review and meta-analysis. Cancers 13, 2496 (2021).
pubmed: 34065365
pmcid: 8160701
doi: 10.3390/cancers13102496
Mossanen, M. et al. Evaluating the cost of surveillance for non-muscle-invasive bladder cancer: an analysis based on risk categories. World J. Urol. 37, 2059–2065 (2019).
pubmed: 30446799
doi: 10.1007/s00345-018-2550-x
Fernandez-Gomez, J. et al. Predicting nonmuscle invasive bladder cancer recurrence and progression in patients treated with bacillus Calmette-Guerin: the CUETO scoring model. J. Urol. 182, 2195–2203 (2009).
pubmed: 19758621
doi: 10.1016/j.juro.2009.07.016
Chang, S. S. et al. Diagnosis and treatment of non-muscle invasive bladder cancer: AUA/SUO guideline. J. Urol. 196, 1021–1029 (2016).
pubmed: 27317986
doi: 10.1016/j.juro.2016.06.049
Soukup, V. et al. Prognostic performance and reproducibility of the 1973 and 2004/2016 World Health Organization grading classification systems in non-muscle-invasive bladder cancer: a European Association of Urology non-muscle invasive bladder cancer guidelines panel systematic review. Eur. Urol. 72, 801–813 (2017).
pubmed: 28457661
doi: 10.1016/j.eururo.2017.04.015
Cambier, S. et al. EORTC nomograms and risk groups for predicting recurrence, progression, and disease-specific and overall survival in non-muscle-invasive stage Ta-T1 urothelial bladder cancer patients treated with 1–3 years of maintenance bacillus Calmette-Guerin. Eur. Urol. 69, 60–69 (2016).
pubmed: 26210894
doi: 10.1016/j.eururo.2015.06.045
Rieken, M. et al. Comparison of the EORTC tables and the EAU categories for risk stratification of patients with nonmuscle-invasive bladder cancer. Urol. Oncol. 36, 8.e17–8.e24 (2018).
pubmed: 28947304
doi: 10.1016/j.urolonc.2017.08.027
Krajewski, W. et al. Accuracy of the CUETO, EORTC 2016 and EAU 2021 scoring models and risk stratification tables to predict outcomes in high-grade non-muscle-invasive urothelial bladder cancer. Urol. Oncol. 40, 491.e11–491.e19 (2022).
pubmed: 35851185
doi: 10.1016/j.urolonc.2022.06.008
Lobo, N. et al. Updated European Association of Urology (EAU) prognostic factor risk groups overestimate the risk of progression in patients with non-muscle-invasive bladder cancer treated with bacillus Calmette-Guerin. Eur. Urol. Oncol. 5, 84–91 (2022).
pubmed: 34920986
doi: 10.1016/j.euo.2021.11.006
Guerrero-Ramos, F. et al. Predicting recurrence and progression in patients with non-muscle-invasive bladder cancer: systematic review on the performance of risk stratification models. Bladder Cancer 8, 339–357 (2022).
pubmed: 38994181
pmcid: 11181743
doi: 10.3233/BLC-220055
Soukup, V. et al. Risk stratification tools and prognostic models in non-muscle-invasive bladder cancer: a critical assessment from the European Association of Urology non-muscle-invasive bladder cancer guidelines panel. Eur. Urol. Focus. 6, 479–489 (2020).
pubmed: 30470647
doi: 10.1016/j.euf.2018.11.005
Jobczyk, M., Stawiski, K., Fendler, W. & Rozanski, W. Validation of EORTC, CUETO, and EAU risk stratification in prediction of recurrence, progression, and death of patients with initially non-muscle-invasive bladder cancer (NMIBC): a cohort analysis. Cancer Med. 9, 4014–4025 (2020).
pubmed: 32216043
pmcid: 7286464
doi: 10.1002/cam4.3007
Cordon-Cardo, C. et al. Altered expression of the retinoblastoma gene product: prognostic indicator in bladder cancer. J. Natl Cancer Inst. 84, 1251–1256 (1992).
pubmed: 1640484
doi: 10.1093/jnci/84.16.1251
Sarkis, A. S. et al. Nuclear overexpression of p53 protein in transitional cell bladder carcinoma: a marker for disease progression. J. Natl Cancer Inst. 85, 53–59 (1993).
pubmed: 7677935
doi: 10.1093/jnci/85.1.53
Casadevall, D., Kilian, A. Y. & Bellmunt, J. The prognostic role of epigenetic dysregulation in bladder cancer: a systematic review. Cancer Treat. Rev. 61, 82–93 (2017).
pubmed: 29121502
doi: 10.1016/j.ctrv.2017.10.004
Birkenkamp-Demtroder, K. et al. Genomic alterations in liquid biopsies from patients with bladder cancer. Eur. Urol. 70, 75–82 (2016).
pubmed: 26803478
doi: 10.1016/j.eururo.2016.01.007
De Carlo, C., Valeri, M., Corbitt, D. N., Cieri, M. & Colombo, P. Non-muscle invasive bladder cancer biomarkers beyond morphology. Front. Oncol. 12, 947446 (2022).
pubmed: 35992775
pmcid: 9382689
doi: 10.3389/fonc.2022.947446
Pepe, M. S. et al. Phases of biomarker development for early detection of cancer. J. Natl Cancer Inst. 93, 1054–1061 (2001).
pubmed: 11459866
doi: 10.1093/jnci/93.14.1054
Liu, J., Peng, Y. & Wei, W. Cell cycle on the crossroad of tumorigenesis and cancer therapy. Trends Cell Biol. 32, 30–44 (2022).
pubmed: 34304958
doi: 10.1016/j.tcb.2021.07.001
Hurst, C. D. et al. Stage-stratified molecular profiling of non-muscle-invasive bladder cancer enhances biological, clinical, and therapeutic insight. Cell Rep. Med. 2, 100472 (2021).
pubmed: 35028613
pmcid: 8714941
doi: 10.1016/j.xcrm.2021.100472
Mitra, A. P., Birkhahn, M. & Cote, R. J. p53 and retinoblastoma pathways in bladder cancer. World J. Urol. 25, 563–571 (2007).
pubmed: 17710407
doi: 10.1007/s00345-007-0197-0
Sjodahl, G. et al. Molecular changes during progression from nonmuscle invasive to advanced urothelial carcinoma. Int. J. Cancer 146, 2636–2647 (2020).
pubmed: 31609466
doi: 10.1002/ijc.32737
Gatti, V., Fierro, C., Annicchiarico-Petruzzelli, M., Melino, G. & Peschiaroli, A. DeltaNp63 in squamous cell carcinoma: defining the oncogenic routes affecting epigenetic landscape and tumour microenvironment. Mol. Oncol. 13, 981–1001 (2019).
pubmed: 30845357
pmcid: 6487733
doi: 10.1002/1878-0261.12473
Choi, W. et al. Identification of distinct basal and luminal subtypes of muscle-invasive bladder cancer with different sensitivities to frontline chemotherapy. Cancer Cell 25, 152–165 (2014).
pubmed: 24525232
pmcid: 4011497
doi: 10.1016/j.ccr.2014.01.009
Papadimitriou, M. A. et al. DeltaNp63 transcript loss in bladder cancer constitutes an independent molecular predictor of TaT1 patients post-treatment relapse and progression. J. Cancer Res. Clin. Oncol. 145, 3075–3087 (2019).
pubmed: 31595333
doi: 10.1007/s00432-019-03028-5
Urist, M. J. et al. Loss of p63 expression is associated with tumor progression in bladder cancer. Am. J. Pathol. 161, 1199–1206 (2002).
pubmed: 12368193
pmcid: 1867279
doi: 10.1016/S0002-9440(10)64396-9
Gaya, J. M. et al. ΔNp63 expression is a protective factor of progression in clinical high grade T1 bladder cancer. J. Urol. 193, 1144–1150 (2015).
pubmed: 25444981
doi: 10.1016/j.juro.2014.10.098
Khan, F. M. et al. Unraveling a tumor type-specific regulatory core underlying E2F1-mediated epithelial-mesenchymal transition to predict receptor protein signatures. Nat. Commun. 8, 198 (2017).
pubmed: 28775339
pmcid: 5543083
doi: 10.1038/s41467-017-00268-2
Mun, J. Y. et al. E2F1 promotes progression of bladder cancer by modulating rad54l involved in homologous recombination repair. Int. J. Mol. Sci. 21, 9025 (2020).
pubmed: 33261027
pmcid: 7730422
doi: 10.3390/ijms21239025
Robertson, A. G. et al. Identification of differential tumor subtypes of T1 bladder cancer. Eur. Urol. 78, 533–537 (2020).
pubmed: 32684305
doi: 10.1016/j.eururo.2020.06.048
Lee, J. S. et al. Expression signature of E2F1 and its associated genes predict superficial to invasive progression of bladder tumors. J. Clin. Oncol. 28, 2660–2667 (2010).
pubmed: 20421545
doi: 10.1200/JCO.2009.25.0977
Song, B.-N. et al. Identification of an immunotherapy-responsive molecular subtype of bladder cancer. eBioMedicine 50, 238–245 (2019).
pubmed: 31735557
pmcid: 6921227
doi: 10.1016/j.ebiom.2019.10.058
Kim, S. K. et al. A molecular signature determines the prognostic and therapeutic subtype of non-muscle-invasive bladder cancer responsive to intravesical bacillus Calmette-Guerin therapy. Int. J. Mol. Sci. 22, 1450 (2021).
pubmed: 33535616
pmcid: 7867154
doi: 10.3390/ijms22031450
Feber, A. et al. Amplification and overexpression of E2F3 in human bladder cancer. Oncogene 23, 1627–1630 (2004).
pubmed: 14716298
doi: 10.1038/sj.onc.1207274
Oeggerli, M. et al. E2F3 amplification and overexpression is associated with invasive tumor growth and rapid tumor cell proliferation in urinary bladder cancer. Oncogene 23, 5616–5623 (2004).
pubmed: 15122326
doi: 10.1038/sj.onc.1207749
Hurst, C. D., Tomlinson, D. C., Williams, S. V., Platt, F. M. & Knowles, M. A. Inactivation of the Rb pathway and overexpression of both isoforms of E2F3 are obligate events in bladder tumours with 6p22 amplification. Oncogene 27, 2716–2727 (2008).
pubmed: 18037967
doi: 10.1038/sj.onc.1210934
Cheng, C., Varn, F. S. & Marsit, C. J. E2F4 program is predictive of progression and intravesical immunotherapy efficacy in bladder cancer. Mol. Cancer Res. 13, 1316–1324 (2015).
pubmed: 26032289
pmcid: 4734892
doi: 10.1158/1541-7786.MCR-15-0120
Lindskrog, S. V. et al. An integrated multi-omics analysis identifies prognostic molecular subtypes of non-muscle-invasive bladder cancer. Nat. Commun. 12, 2301 (2021).
pubmed: 33863885
pmcid: 8052448
doi: 10.1038/s41467-021-22465-w
Ramesh, N. et al. CG0070, a conditionally replicating granulocyte macrophage colony-stimulating factor-armed oncolytic adenovirus for the treatment of bladder cancer. Clin. Cancer Res. 12, 305–313 (2006).
pubmed: 16397056
doi: 10.1158/1078-0432.CCR-05-1059
Packiam, V. T. et al. An open label, single-arm, phase II multicenter study of the safety and efficacy of CG0070 oncolytic vector regimen in patients with BCG-unresponsive non-muscle-invasive bladder cancer: interim results. Urol. Oncol. 36, 440–447 (2018).
pubmed: 28755959
doi: 10.1016/j.urolonc.2017.07.005
US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/study/NCT04452591 (2024).
Fagundes, R. & Teixeira, L. K. Cyclin E/CDK2: DNA replication, replication stress and genomic instability. Front. Cell Dev. Biol. 9, 774845 (2021).
pubmed: 34901021
pmcid: 8652076
doi: 10.3389/fcell.2021.774845
Zhao, H. et al. Prognostic values of CCNE1 amplification and overexpression in cancer patients: a systematic review and meta-analysis. J. Cancer 9, 2397–2407 (2018).
pubmed: 30026836
pmcid: 6036712
doi: 10.7150/jca.24179
Bellmunt, J. et al. Genomic predictors of good outcome, recurrence, or progression in high-grade T1 non-muscle-invasive bladder cancer. Cancer Res. 80, 4476–4486 (2020).
pubmed: 32868381
pmcid: 9361191
doi: 10.1158/0008-5472.CAN-20-0977
Bacon, J. V. W. et al. Somatic features of response and relapse in non-muscle-invasive bladder cancer treated with bacillus Calmette-Guerin immunotherapy. Eur. Urol. Oncol. 5, 677–686 (2022).
pubmed: 34895867
doi: 10.1016/j.euo.2021.11.002
Song, B. N., Kim, S. K. & Chu, I. S. Bioinformatic identification of prognostic signature defined by copy number alteration and expression of CCNE1 in non-muscle invasive bladder cancer. Exp. Mol. Med. 49, e282 (2017).
pubmed: 28082741
pmcid: 5291834
doi: 10.1038/emm.2016.120
Le Goux, C. et al. Assessment of prognostic implication of a panel of oncogenes in bladder cancer and identification of a 3-gene signature associated with recurrence and progression risk in non-muscle-invasive bladder cancer. Sci. Rep. 10, 16641 (2020).
pubmed: 33024200
pmcid: 7538919
doi: 10.1038/s41598-020-73642-8
Wee, S. et al. Discovery of INCB123667, a potent and selective cyclin-dependent kinase 2 (CDK2) inhibitor for the treatment of cyclin E dysregulated cancers. Eur. J. Cancer 174, S79 (2022).
doi: 10.1016/S0959-8049(22)01010-3
Wang, Y. Phase 1/2 study of ARTS-021, a potent, oral administrated, selective CDK2 inhibitor, in advanced or metastatic solid tumors. J. Clin. Oncol. 41, e17546–e17546 (2023).
doi: 10.1200/JCO.2023.41.16_suppl.e17546
Beck, H. et al. Cyclin-dependent kinase suppression by WEE1 kinase protects the genome through control of replication initiation and nucleotide consumption. Mol. Cell Biol. 32, 4226–4236 (2012).
pubmed: 22907750
pmcid: 3457333
doi: 10.1128/MCB.00412-12
Aarts, M. et al. Forced mitotic entry of S-phase cells as a therapeutic strategy induced by inhibition of WEE1. Cancer Discov. 2, 524–539 (2012).
pubmed: 22628408
doi: 10.1158/2159-8290.CD-11-0320
Mir, S. E. et al. In silico analysis of kinase expression identifies WEE1 as a gatekeeper against mitotic catastrophe in glioblastoma. Cancer Cell 18, 244–257 (2010).
pubmed: 20832752
pmcid: 3115571
doi: 10.1016/j.ccr.2010.08.011
Murakami, K. et al. Antitumor effect of WEE1 blockade as monotherapy or in combination with cisplatin in urothelial cancer. Cancer Sci. 112, 3669–3681 (2021).
pubmed: 34212455
pmcid: 8409401
doi: 10.1111/cas.15051
Fu, S. et al. Multicenter phase II trial of the WEE1 inhibitor adavosertib in refractory solid tumors harboring CCNE1 amplification. J. Clin. Oncol. 41, 1725–1734 (2023).
pubmed: 36469840
doi: 10.1200/JCO.22.00830
Goel, S., Bergholz, J. S. & Zhao, J. J. Targeting CDK4 and CDK6 in cancer. Nat. Rev. Cancer 22, 356–372 (2022).
pubmed: 35304604
pmcid: 9149100
doi: 10.1038/s41568-022-00456-3
Zhao, R., Choi, B. Y., Lee, M. H., Bode, A. M. & Dong, Z. Implications of genetic and epigenetic alterations of CDKN2A (p16
pubmed: 27428416
pmcid: 4919535
doi: 10.1016/j.ebiom.2016.04.017
Bartlett, J. M. et al. Is chromosome 9 loss a marker of disease recurrence in transitional cell carcinoma of the urinary bladder? Br. J. Cancer 77, 2193–2198 (1998).
pubmed: 9649132
pmcid: 2150395
doi: 10.1038/bjc.1998.365
Tsukamoto, M. et al. Numerical aberrations of chromosome 9 in bladder cancer. A possible prognostic marker for early tumor recurrence. Cancer Genet. Cytogenet. 134, 41–45 (2002).
pubmed: 11996795
doi: 10.1016/S0165-4608(01)00618-5
Meeks, J. J. et al. Genomic characterization of high-risk non-muscle invasive bladder cancer. Oncotarget 7, 75176–75184 (2016).
pubmed: 27750214
pmcid: 5342732
doi: 10.18632/oncotarget.12661
Jung, I. et al. Chromosome 9 monosomy by fluorescence in situ hybridization of bladder irrigation specimens is predictive of tumor recurrence. J. Urol. 162, 1900–1903 (1999).
pubmed: 10569533
doi: 10.1016/S0022-5347(05)68064-0
Rebouissou, S. et al. CDKN2A homozygous deletion is associated with muscle invasion in FGFR3-mutated urothelial bladder carcinoma. J. Pathol. 227, 315–324 (2012).
pubmed: 22422578
doi: 10.1002/path.4017
Ploussard, G. et al. The prognostic value of FGFR3 mutational status for disease recurrence and progression depends on allelic losses at 9p22. Am. J. Cancer Res. 1, 498–507 (2011).
pubmed: 21984968
pmcid: 3186048
Breyer, J. et al. High CDKN2A/p16 and low FGFR3 expression predict progressive potential of stage pT1 urothelial bladder carcinoma. Clin. Genitourin. Cancer 16, 248–256.e2 (2018).
pubmed: 29525349
doi: 10.1016/j.clgc.2018.01.009
Sikic, D. et al. The prognostic value of FGFR3 expression in patients with T1 non-muscle invasive bladder cancer. Cancer Manag. Res. 13, 6567–6578 (2021).
pubmed: 34447272
pmcid: 8384147
doi: 10.2147/CMAR.S318893
Rubio, C. et al. CDK4/6 inhibitor as a novel therapeutic approach for advanced bladder cancer independently of RB1 status. Clin. Cancer Res. 25, 390–402 (2019).
pubmed: 30242024
doi: 10.1158/1078-0432.CCR-18-0685
US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/study/NCT03837821 (2024).
US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/study/NCT04887831 (2024).
Solomon, D. A. et al. Frequent truncating mutations of STAG2 in bladder cancer. Nat. Genet. 45, 1428–1430 (2013).
pubmed: 24121789
pmcid: 3875130
doi: 10.1038/ng.2800
Balbas-Martinez, C. et al. Recurrent inactivation of STAG2 in bladder cancer is not associated with aneuploidy. Nat. Genet. 45, 1464–1469 (2013).
pubmed: 24121791
pmcid: 3840052
doi: 10.1038/ng.2799
Taylor, C. F., Platt, F. M., Hurst, C. D., Thygesen, H. H. & Knowles, M. A. Frequent inactivating mutations of STAG2 in bladder cancer are associated with low tumour grade and stage and inversely related to chromosomal copy number changes. Hum. Mol. Genet. 23, 1964–1974 (2014).
pubmed: 24270882
doi: 10.1093/hmg/ddt589
Pietzak, E. J. et al. Next-generation sequencing of nonmuscle invasive bladder cancer reveals potential biomarkers and rational therapeutic targets. Eur. Urol. 72, 952–959 (2017).
pubmed: 28583311
pmcid: 6007852
doi: 10.1016/j.eururo.2017.05.032
Shao, Y. et al. Prognostic factors of non-muscle invasive bladder cancer: a study based on next-generation sequencing. Cancer Cell Int. 21, 23 (2021).
pubmed: 33407469
pmcid: 7789352
doi: 10.1186/s12935-020-01731-9
Gordon, N. S. et al. STAG2 protein expression in non-muscle-invasive bladder cancer: associations with sex, genomic and transcriptomic changes, and clinical outcomes. Eur. Urol. Open. Sci. 38, 88–95 (2022).
pubmed: 35495284
pmcid: 9051973
doi: 10.1016/j.euros.2022.02.004
Taber, A. et al. STAG2 as a prognostic biomarker in low-grade non-muscle invasive bladder cancer. Urol. Oncol. 39, 438.e1–438.e9 (2021).
pubmed: 33712344
doi: 10.1016/j.urolonc.2021.02.007
Lelo, A. et al. STAG2 is a biomarker for prediction of recurrence and progression in papillary non-muscle-invasive bladder cancer. Clin. Cancer Res. 24, 4145–4153 (2018).
pubmed: 29954776
pmcid: 6125225
doi: 10.1158/1078-0432.CCR-17-3244
Rinaldetti, S. et al. FOXM1 predicts disease progression in non-muscle invasive bladder cancer. J. Cancer Res. Clin. Oncol. 144, 1701–1709 (2018).
pubmed: 29959570
pmcid: 6096766
doi: 10.1007/s00432-018-2694-5
Breyer, J. et al. FOXM1 overexpression is associated with adverse outcome and predicts response to intravesical instillation therapy in stage pT1 non-muscle-invasive bladder cancer. BJU Int. 123, 187–196 (2019).
pubmed: 30120861
doi: 10.1111/bju.14525
Shi, J., Zhang, P., Liu, L., Min, X. & Xiao, Y. Weighted gene coexpression network analysis identifies a new biomarker of CENPF for prediction disease prognosis and progression in nonmuscle invasive bladder cancer. Mol. Genet. Genom. Med. 7, e982 (2019).
doi: 10.1002/mgg3.982
Lin, S. C. et al. Dysregulation of miRNAs-COUP-TFII-FOXM1-CENPF axis contributes to the metastasis of prostate cancer. Nat. Commun. 7, 11418 (2016).
pubmed: 27108958
pmcid: 4848536
doi: 10.1038/ncomms11418
Aytes, A. et al. Cross-species regulatory network analysis identifies a synergistic interaction between FOXM1 and CENPF that drives prostate cancer malignancy. Cancer Cell 25, 638–651 (2014).
pubmed: 24823640
pmcid: 4051317
doi: 10.1016/j.ccr.2014.03.017
Khan, M. A., Khan, P., Ahmad, A., Fatima, M. & Nasser, M. W. FOXM1: a small fox that makes more tracks for cancer progression and metastasis. Semin. Cancer Biol. 92, 1–15 (2023).
pubmed: 36958703
pmcid: 10199453
doi: 10.1016/j.semcancer.2023.03.007
Jeyaprakash, A. A. et al. Structural and functional organization of the Ska complex, a key component of the kinetochore-microtubule interface. Mol. Cell 46, 274–286 (2012).
pubmed: 22483620
doi: 10.1016/j.molcel.2012.03.005
Gaitanos, T. N. et al. Stable kinetochore-microtubule interactions depend on the Ska complex and its new component Ska3/C13Orf3. EMBO J. 28, 1442–1452 (2009).
pubmed: 19360002
pmcid: 2669960
doi: 10.1038/emboj.2009.96
Li, J. et al. SKA1 over-expression promotes centriole over-duplication, centrosome amplification and prostate tumourigenesis. J. Pathol. 234, 178–189 (2014).
pubmed: 24827423
doi: 10.1002/path.4374
Jiang, S. et al. High expression of spindle and kinetochore-associated protein 1 predicts early recurrence and progression of non-muscle invasive bladder cancer. Cancer Biomark. 22, 543–549 (2018).
pubmed: 29865039
doi: 10.3233/CBM-181202
Li, Z. et al. Immunological role and prognostic value of the SKA family in pan-cancer analysis. Front. Immunol. 14, 1012999 (2023).
pubmed: 37180139
pmcid: 10169755
doi: 10.3389/fimmu.2023.1012999
Lan, H. et al. Pancancer analysis of SKA1 mutation and its association with the diagnosis and prognosis of human cancers. Genomics 115, 110554 (2023).
pubmed: 36587749
doi: 10.1016/j.ygeno.2022.110554
Wang, C. et al. SKA3 is a prognostic biomarker and associated with immune infiltration in bladder cancer. Hereditas 159, 20 (2022).
pubmed: 35546682
pmcid: 9092687
doi: 10.1186/s41065-022-00234-z
You, C., Piao, X. M., Kang, K., Kim, Y. J. & Kang, K. Integrative transcriptome profiling reveals SKA3 as a novel prognostic marker in non-muscle invasive bladder cancer. Cancers 13, 4673 (2021).
pubmed: 34572901
pmcid: 8470398
doi: 10.3390/cancers13184673
Dhillon, A. S., Hagan, S., Rath, O. & Kolch, W. MAP kinase signalling pathways in cancer. Oncogene 26, 3279–3290 (2007).
pubmed: 17496922
doi: 10.1038/sj.onc.1210421
Katoh, M. & Nakagama, H. FGF receptors: cancer biology and therapeutics. Med. Res. Rev. 34, 280–300 (2014).
pubmed: 23696246
doi: 10.1002/med.21288
Hernandez, 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
van Rhijn, B. W. et al. Molecular grade (FGFR3/MIB-1) and EORTC risk scores are predictive in primary non-muscle-invasive bladder cancer. Eur. Urol. 58, 433–441 (2010).
pubmed: 20646825
doi: 10.1016/j.eururo.2010.05.043
Burger, M. et al. Prediction of progression of non-muscle-invasive bladder cancer by WHO 1973 and 2004 grading and by FGFR3 mutation status: a prospective study. Eur. Urol. 54, 835–843 (2008).
pubmed: 18166262
doi: 10.1016/j.eururo.2007.12.026
van Rhijn, B. W. et al. The FGFR3 mutation is related to favorable pT1 bladder cancer. J. Urol. 187, 310–314 (2012).
pubmed: 22099989
doi: 10.1016/j.juro.2011.09.008
van Rhijn, B. W. G. et al. FGFR3 mutation status and FGFR3 expression in a large bladder cancer cohort treated by radical cystectomy: implications for anti-FGFR3 treatment?(†). Eur. Urol. 78, 682–687 (2020).
pubmed: 32682615
doi: 10.1016/j.eururo.2020.07.002
van Rhijn, B. W. et al. FGFR3 and P53 characterize alternative genetic pathways in the pathogenesis of urothelial cell carcinoma. Cancer Res. 64, 1911–1914 (2004).
pubmed: 15026322
doi: 10.1158/0008-5472.CAN-03-2421
Kang, H. W. et al. Expression levels of FGFR3 as a prognostic marker for the progression of primary pT1 bladder cancer and its association with mutation status. Oncol. Lett. 14, 3817–3824 (2017).
pubmed: 28927152
pmcid: 5587943
doi: 10.3892/ol.2017.6621
van Kessel, K. E. M. et al. Molecular markers increase precision of the European Association of Urology non-muscle-invasive bladder cancer progression risk groups. Clin. Cancer Res. 24, 1586–1593 (2018).
pubmed: 29367430
doi: 10.1158/1078-0432.CCR-17-2719
Ascione, C. M. et al. Role of FGFR3 in bladder cancer: treatment landscape and future challenges. Cancer Treat. Rev. 115, 102530 (2023).
pubmed: 36898352
doi: 10.1016/j.ctrv.2023.102530
Siefker-Radtke, A. O. et al. Efficacy and safety of erdafitinib in patients with locally advanced or metastatic urothelial carcinoma: long-term follow-up of a phase 2 study. Lancet Oncol. 23, 248–258 (2022).
pubmed: 35030333
doi: 10.1016/S1470-2045(21)00660-4
Catto, J. W. F. et al. Erdafitinib in BCG-treated high-risk non-muscle-invasive bladder cancer. Ann. Oncol. 35, 98–106 (2024).
pubmed: 37871701
doi: 10.1016/j.annonc.2023.09.3116
US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/study/NCT03914794 (2024).
Moasser, M. M. The oncogene HER2: its signaling and transforming functions and its role in human cancer pathogenesis. Oncogene 26, 6469–6487 (2007).
pubmed: 17471238
pmcid: 3021475
doi: 10.1038/sj.onc.1210477
Zhao, J. et al. Prognostic role of HER2 expression in bladder cancer: a systematic review and meta-analysis. Int. Urol. Nephrol. 47, 87–94 (2015).
pubmed: 25384433
doi: 10.1007/s11255-014-0866-z
Breyer, J. et al. ERBB2 expression as potential risk-stratification for early cystectomy in patients with pT1 bladder cancer and concomitant carcinoma in situ. Urol. Int. 98, 282–289 (2017).
pubmed: 27992871
doi: 10.1159/000453670
Lim, S. D. et al. Clinical significance of substaging and HER2 expression in papillary nonmuscle invasive urothelial cancers of the urinary bladder. J. Korean Med. Sci. 30, 1068–1077 (2015).
pubmed: 26240484
pmcid: 4520937
doi: 10.3346/jkms.2015.30.8.1068
Tan, X. et al. Prognostic significance of HER2 expression in patients with bacillus Calmette-Guérin-exposed non-muscle-invasive bladder cancer. Eur. Urol. Oncol. https://doi.org/10.1016/j.euo.2023.10.003 (2023).
Kocsmár, I. et al. Addition of chromosome 17 polysomy and HER2 amplification status improves the accuracy of clinicopathological factor-based progression risk stratification and tumor grading of non-muscle-invasive bladder cancer. Cancers 14, 4570 (2022).
pubmed: 36230493
pmcid: 9558547
doi: 10.3390/cancers14194570
Koshkin, V. S., O’Donnell, P., Yu, E. Y. & Grivas, P. Systematic review: targeting HER2 in bladder cancer. Bladder Cancer 5, 1–12 (2019).
doi: 10.3233/BLC-180196
Copeland-Halperin, R. S., Liu, J. E. & Yu, A. F. Cardiotoxicity of HER2-targeted therapies. Curr. Opin. Cardiol. 34, 451–458 (2019).
pubmed: 31082851
pmcid: 7313632
doi: 10.1097/HCO.0000000000000637
Swain, S. M., Shastry, M. & Hamilton, E. Targeting HER2-positive breast cancer: advances and future directions. Nat. Rev. Drug. Discov. 22, 101–126 (2023).
pubmed: 36344672
doi: 10.1038/s41573-022-00579-0
Peters, S. et al. Antibody-drug conjugates in lung and breast cancer: current evidence and future directions — a position statement from the ETOP IBCSG Partners Foundation. Ann. Oncol. 35, 607–629 (2024).
pubmed: 38648979
doi: 10.1016/j.annonc.2024.04.002
Sheng, X. et al. Efficacy and safety of disitamab vedotin in patients with human epidermal growth factor receptor 2-positive locally advanced or metastatic urothelial carcinoma: a combined analysis of two phase II clinical trials. J. Clin. Oncol. 42, 1391–1402 (2024).
pubmed: 37988648
doi: 10.1200/JCO.22.02912
Sheng, X. et al. Open-label, multicenter, phase II study of RC48-ADC, a HER2-targeting antibody-drug conjugate, in patients with locally advanced or metastatic urothelial carcinoma. Clin. Cancer Res. 27, 43–51 (2021).
pubmed: 33109737
doi: 10.1158/1078-0432.CCR-20-2488
Matt, D. G. et al. Primary analysis from DS8201-A-U105: a phase 1b, two-part, open-label study of trastuzumab deruxtecan (T-DXd) with nivolumab (nivo) in patients (pts) with HER2-expressing urothelial carcinoma (UC). J. Clin. Oncol. 40, 438–438 (2022).
doi: 10.1200/JCO.2022.40.6_suppl.438
Shih, C. H., Lin, Y. H., Luo, H. L. & Sung, W. W. Antibody-drug conjugates targeting HER2 for the treatment of urothelial carcinoma: potential therapies for HER2-positive urothelial carcinoma. Front. Pharmacol. 15, 1326296 (2024).
pubmed: 38572425
pmcid: 10987710
doi: 10.3389/fphar.2024.1326296
Zerenturk, E. J., Sharpe, L. J., Ikonen, E. & Brown, A. J. Desmosterol and DHCR24: unexpected new directions for a terminal step in cholesterol synthesis. Prog. Lipid Res. 52, 666–680 (2013).
pubmed: 24095826
doi: 10.1016/j.plipres.2013.09.002
Luu, W. et al. Signaling regulates activity of DHCR24, the final enzyme in cholesterol synthesis. J. Lipid Res. 55, 410–420 (2014).
pubmed: 24363437
pmcid: 3934726
doi: 10.1194/jlr.M043257
Lee, G. T. et al. DHCR24 is an independent predictor of progression in patients with non-muscle-invasive urothelial carcinoma, and its functional role is involved in the aggressive properties of urothelial carcinoma cells. Ann. Surg. Oncol. 21, S538–S545 (2014).
pubmed: 24562935
doi: 10.1245/s10434-014-3560-6
Liu, X. P. et al. DHCR24 predicts poor clinicopathological features of patients with bladder cancer: a STROBE-compliant study. Medicine 97, e11830 (2018).
pubmed: 30278482
pmcid: 6181456
doi: 10.1097/MD.0000000000011830
Korner, A. et al. Inhibition of Δ24-dehydrocholesterol reductase activates pro-resolving lipid mediator biosynthesis and inflammation resolution. Proc. Natl Acad. Sci. USA 116, 20623–20634 (2019).
pubmed: 31548397
pmcid: 6789642
doi: 10.1073/pnas.1911992116
Wu, J. et al. Genkwadaphnin inhibits growth and invasion in hepatocellular carcinoma by blocking DHCR24-mediated cholesterol biosynthesis and lipid rafts formation. Br. J. Cancer 123, 1673–1685 (2020).
pubmed: 32958824
pmcid: 7686505
doi: 10.1038/s41416-020-01085-z
Fang, J., Akaike, T. & Maeda, H. Antiapoptotic role of heme oxygenase (HO) and the potential of HO as a target in anticancer treatment. Apoptosis 9, 27–35 (2004).
pubmed: 14739596
doi: 10.1023/B:APPT.0000012119.83734.4e
Kim, W. J. et al. Predictive value of progression-related gene classifier in primary non-muscle invasive bladder cancer. Mol. Cancer 9, 3 (2010).
pubmed: 20059769
pmcid: 2821358
doi: 10.1186/1476-4598-9-3
Yim, M.-S. et al. HMOX1 is an important prognostic indicator of nonmuscle invasive bladder cancer recurrence and progression. J. Urol. 185, 701–705 (2011).
pubmed: 21168882
doi: 10.1016/j.juro.2010.09.081
Peng, Y. et al. JUND-dependent up-regulation of HMOX1 is associated with cisplatin resistance in muscle-invasive bladder cancer. J. Biochem. 168, 73–82 (2020).
pubmed: 32240302
doi: 10.1093/jb/mvaa027
Miyata, Y., Kanda, S., Mitsunari, K., Asai, A. & Sakai, H. Heme oxygenase-1 expression is associated with tumor aggressiveness and outcomes in patients with bladder cancer: a correlation with smoking intensity. Transl. Res. 164, 468–476 (2014).
pubmed: 25063314
doi: 10.1016/j.trsl.2014.06.010
Matsuo, T. et al. Pathological significance and prognostic implications of heme oxygenase 1 expression in non-muscle-invasive bladder cancer: correlation with cell proliferation, angiogenesis, lymphangiogenesis and expression of VEGFs and COX-2. Oncol. Lett. 13, 275–280 (2017).
pubmed: 28123555
doi: 10.3892/ol.2016.5416
Berberat, P. O. et al. Inhibition of heme oxygenase-1 increases responsiveness of pancreatic cancer cells to anticancer treatment. Clin. Cancer Res. 11, 3790–3798 (2005).
pubmed: 15897578
doi: 10.1158/1078-0432.CCR-04-2159
Zhe, N. et al. Heme oxygenase-1 plays a crucial role in chemoresistance in acute myeloid leukemia. Hematology 20, 384–391 (2015).
pubmed: 26218201
doi: 10.1179/1607845414Y.0000000212
Podkalicka, P., Mucha, O., Jozkowicz, A., Dulak, J. & Loboda, A. Heme oxygenase inhibition in cancers: possible tools and targets. Contemp. Oncol. 22, 23–32 (2018).
Alfano, M. et al. The interplay of extracellular matrix and microbiome in urothelial bladder cancer. Nat. Rev. Urol. 13, 77–90 (2016).
pubmed: 26666363
doi: 10.1038/nrurol.2015.292
Strandgaard, T. et al. Elevated T-cell exhaustion and urinary tumor DNA levels are associated with bacillus Calmette-Guerin failure in patients with non-muscle-invasive bladder cancer. Eur. Urol. 82, 646–656 (2022).
pubmed: 36210217
doi: 10.1016/j.eururo.2022.09.008
Inman, B. A. et al. PD-L1 (B7-H1) expression by urothelial carcinoma of the bladder and BCG-induced granulomata: associations with localized stage progression. Cancer 109, 1499–1505 (2007).
pubmed: 17340590
doi: 10.1002/cncr.22588
Lee, Y. C. et al. The dynamic roles of the bladder tumour microenvironment. Nat. Rev. Urol. 19, 515–533 (2022).
pubmed: 35764795
pmcid: 10112172
doi: 10.1038/s41585-022-00608-y
Dong, H. et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat. Med. 8, 793–800 (2002).
pubmed: 12091876
doi: 10.1038/nm730
Nakanishi, J. et al. Overexpression of B7-H1 (PD-L1) significantly associates with tumor grade and postoperative prognosis in human urothelial cancers. Cancer Immunol. Immunother. 56, 1173–1182 (2007).
pubmed: 17186290
doi: 10.1007/s00262-006-0266-z
Le Goux, C. et al. Correlation between messenger RNA expression and protein expression of immune checkpoint-associated molecules in bladder urothelial carcinoma: a retrospective study. Urol. Oncol. 35, 257–263 (2017).
pubmed: 28291636
doi: 10.1016/j.urolonc.2017.01.014
Taber, A. et al. Immune contexture and differentiation features predict outcome in bladder cancer. Eur. Urol. Oncol. 5, 203–213 (2022).
pubmed: 35227680
doi: 10.1016/j.euo.2022.01.008
Breyer, J. et al. High PDL1 mRNA expression predicts better survival of stage pT1 non-muscle-invasive bladder cancer (NMIBC) patients. Cancer Immunol. Immunother. 67, 403–412 (2018).
pubmed: 29150702
doi: 10.1007/s00262-017-2093-9
Kawahara, T. et al. PD-1 and PD-L1 are more highly expressed in high-grade bladder cancer than in low-grade cases: PD-L1 might function as a mediator of stage progression in bladder cancer. BMC Urol. 18, 97 (2018).
pubmed: 30400941
pmcid: 6219206
doi: 10.1186/s12894-018-0414-8
Huang, Y. et al. The prognostic significance of PD-L1 in bladder cancer. Oncol. Rep. 33, 3075–3084 (2015).
pubmed: 25963805
doi: 10.3892/or.2015.3933
Nowak, Ł., Krajewski, W., Poterek, A., Śliwa, A. & Zdrojowy, R. The prognostic value of programmed cell death protein ligand 1 in patients with non-muscle-invasive bladder cancer treated with bacille Calmette–Guérin immunotherapy: current status. Arab. J. Urol. 19, 67–70 (2021).
doi: 10.1080/2090598X.2020.1791562
Balar, A. V. et al. Pembrolizumab monotherapy for the treatment of high-risk non-muscle-invasive bladder cancer unresponsive to BCG (KEYNOTE-057): an open-label, single-arm, multicentre, phase 2 study. Lancet Oncol. 22, 919–930 (2021).
pubmed: 34051177
doi: 10.1016/S1470-2045(21)00147-9
Andrea, N. et al. Pembrolizumab (pembro) monotherapy for patients (pts) with high-risk non-muscle-invasive bladder cancer (HR NMIBC) unresponsive to bacillus Calmette–Guérin (BCG): results from cohort B of the phase 2 KEYNOTE-057 trial. J. Clin. Oncol. 41, LBA442–LBA442 (2023).
doi: 10.1200/JCO.2023.41.6_suppl.LBA442
Black, P. C. et al. Phase 2 trial of atezolizumab in bacillus Calmette-Guérin-unresponsive high-risk non-muscle-invasive bladder cancer: SWOG S1605. Eur. Urol. 84, 536–544 (2023).
pubmed: 37596191
doi: 10.1016/j.eururo.2023.08.004
Hahn, N. M. et al. A phase 1 trial of durvalumab in combination with bacillus Calmette-Guerin (BCG) or external beam radiation therapy in patients with BCG-unresponsive non-muscle-invasive bladder cancer: the Hoosier Cancer Research Network GU16-243 ADAPT-BLADDER study. Eur. Urol. 83, 486–494 (2023).
pubmed: 36717286
pmcid: 10192088
doi: 10.1016/j.eururo.2023.01.017
Li, R. et al. A phase II study of durvalumab for bacillus Calmette-Guerin (BCG) unresponsive urothelial carcinoma in situ of the bladder. Clin. Cancer Res. 29, 3875–3881 (2023).
pubmed: 37505486
doi: 10.1158/1078-0432.CCR-23-0354
US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/study/NCT03528694 (2024).
US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/study/NCT05943106 (2024).
US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/study/NCT03892642 (2024).
de Jong, F. C., Rutten, V. C., Zuiverloon, T. C. M. & Theodorescu, D. Improving anti-PD-1/PD-L1 therapy for localized bladder cancer. Int. J. Mol. Sci. 22, 2800 (2021).
pubmed: 33802033
pmcid: 7998260
doi: 10.3390/ijms22062800
Hannouneh, Z. A. et al. Novel immunotherapeutic options for BCG-unresponsive high-risk non-muscle-invasive bladder cancer. Cancer Med. 12, 21944–21968 (2023).
pubmed: 38037752
pmcid: 10757155
doi: 10.1002/cam4.6768
Hazini, A., Fisher, K. & Seymour, L. Deregulation of HLA-I in cancer and its central importance for immunotherapy. J. Immunother. Cancer 9, e002899 (2021).
pubmed: 34353849
pmcid: 8344275
doi: 10.1136/jitc-2021-002899
Aptsiauri, N. & Garrido, F. The challenges of HLA class I loss in cancer immunotherapy: facts and hopes. Clin. Cancer Res. 28, 5021–5029 (2022).
pubmed: 35861868
doi: 10.1158/1078-0432.CCR-21-3501
Gil-Julio, H. et al. Tumor escape phenotype in bladder cancer is associated with loss of HLA class I expression, T-cell exclusion and stromal changes. Int. J. Mol. Sci. 22, 7248 (2021).
pubmed: 34298868
pmcid: 8307653
doi: 10.3390/ijms22147248
Yi, R. et al. MHC-II signature correlates with anti-tumor immunity and predicts anti-PD-L1 response of bladder cancer. Front. Cell Dev. Biol. 10, 757137 (2022).
pubmed: 35223828
pmcid: 8873787
doi: 10.3389/fcell.2022.757137
Piao, X. M. et al. A prognostic immune predictor, HLA-DRA, plays diverse roles in non-muscle invasive and muscle invasive bladder cancer. Urol. Oncol. 39, 237.e21–237.e29 (2021).
pubmed: 33339725
doi: 10.1016/j.urolonc.2020.11.017
de Jong, F. C. et al. Non-muscle-invasive bladder cancer molecular subtypes predict differential response to intravesical Bacillus Calmette-Guerin. Sci. Transl. Med. 15, eabn4118 (2023).
pubmed: 37224225
pmcid: 10572776
doi: 10.1126/scitranslmed.abn4118
Brabletz, S., Schuhwerk, H., Brabletz, T. & Stemmler, M. P. Dynamic EMT: a multi-tool for tumor progression. EMBO J. 40, e108647 (2021).
pubmed: 34459003
pmcid: 8441439
doi: 10.15252/embj.2021108647
Banerjee, S. et al. Multiple roles for basement membrane proteins in cancer progression and EMT. Eur. J. Cell Biol. 101, 151220 (2022).
pubmed: 35366585
doi: 10.1016/j.ejcb.2022.151220
Zhu, H., Chen, H., Wang, J., Zhou, L. & Liu, S. Collagen stiffness promoted non-muscle-invasive bladder cancer progression to muscle-invasive bladder cancer. Onco Targets Ther. 12, 3441–3457 (2019).
pubmed: 31123405
pmcid: 6511250
doi: 10.2147/OTT.S194568
Brooks, M. et al. Positive association of collagen type I with non-muscle invasive bladder cancer progression. Oncotarget 7, 82609–82619 (2016).
pubmed: 27655672
pmcid: 5347718
doi: 10.18632/oncotarget.12089
Tsai, M. C. et al. DDR2 overexpression in urothelial carcinoma indicates an unfavorable prognosis: a large cohort study. Oncotarget 7, 78918–78931 (2016).
pubmed: 27793038
pmcid: 5346687
doi: 10.18632/oncotarget.12912
Cyrenne, J. B. et al. Comprehensive gene sequencing to identify progression predictors to muscle-invasive bladder cancer. J. Clin. Oncol. 41, 570–570 (2023).
doi: 10.1200/JCO.2023.41.6_suppl.570
Chen, Z. et al. Single-cell RNA sequencing highlights the role of inflammatory cancer-associated fibroblasts in bladder urothelial carcinoma. Nat. Commun. 11, 5077 (2020).
pubmed: 33033240
pmcid: 7545162
doi: 10.1038/s41467-020-18916-5
Wang, L. et al. EMT- and stroma-related gene expression and resistance to PD-1 blockade in urothelial cancer. Nat. Commun. 9, 3503 (2018).
pubmed: 30158554
pmcid: 6115401
doi: 10.1038/s41467-018-05992-x
Tu, M. M. et al. Targeting DDR2 enhances tumor response to anti-PD-1 immunotherapy. Sci. Adv. 5, eaav2437 (2019).
pubmed: 30801016
pmcid: 6382401
doi: 10.1126/sciadv.aav2437
You, S. et al. Discoidin domain receptor-driven gene signatures as markers of patient response to anti-PD-L1 immune checkpoint therapy. J. Natl Cancer Inst. 114, 1380–1391 (2022).
pubmed: 35918812
pmcid: 9552307
doi: 10.1093/jnci/djac140
Alexandrov, L. B. et al. Signatures of mutational processes in human cancer. Nature 500, 415–421 (2013).
pubmed: 23945592
pmcid: 3776390
doi: 10.1038/nature12477
Nassar, A. H. et al. Mutational analysis of 472 urothelial carcinoma across grades and anatomic sites. Clin. Cancer Res. 25, 2458–2470 (2019).
pubmed: 30593515
doi: 10.1158/1078-0432.CCR-18-3147
Bakr, A. et al. ARID1A regulates DNA repair through chromatin organization and its deficiency triggers DNA damage-mediated anti-tumor immune response. Nucleic Acids Res. 52, 5698–5719 (2024).
pubmed: 38587186
pmcid: 11162808
doi: 10.1093/nar/gkae233
Balbas-Martinez, C. et al. ARID1A alterations are associated with FGFR3-wild type, poor-prognosis, urothelial bladder tumors. PLoS ONE 8, e62483 (2013).
pubmed: 23650517
pmcid: 3641081
doi: 10.1371/journal.pone.0062483
Strandgaard, T. et al. Field cancerization is associated with tumor development, T-cell exhaustion, and clinical outcomes in bladder cancer. Eur. Urol. 85, 82–92 (2023).
pubmed: 37718188
doi: 10.1016/j.eururo.2023.07.014
Lawson, A. R. J. et al. Extensive heterogeneity in somatic mutation and selection in the human bladder. Science 370, 75–82 (2020).
pubmed: 33004514
doi: 10.1126/science.aba8347
Bastos, D. A. et al. Genomic biomarkers and underlying mechanism of benefit from BCG immunotherapy in non-muscle invasive bladder cancer. Bladder Cancer 6, 171–186 (2020).
doi: 10.3233/BLC-200289
Mandal, J., Mandal, P., Wang, T.-L. & Shih, I.-M. Treating ARID1A mutated cancers by harnessing synthetic lethality and DNA damage response. J. Biomed. Sci. 29, 71 (2022).
pubmed: 36123603
pmcid: 9484255
doi: 10.1186/s12929-022-00856-5
Marteijn, J. A., Lans, H., Vermeulen, W. & Hoeijmakers, J. H. Understanding nucleotide excision repair and its roles in cancer and ageing. Nat. Rev. Mol. Cell Biol. 15, 465–481 (2014).
pubmed: 24954209
doi: 10.1038/nrm3822
Kim, J. et al. Somatic ERCC2 mutations are associated with a distinct genomic signature in urothelial tumors. Nat. Genet. 48, 600–606 (2016).
pubmed: 27111033
pmcid: 4936490
doi: 10.1038/ng.3557
Li, Q. et al. ERCC2 helicase domain mutations confer nucleotide excision repair deficiency and drive cisplatin sensitivity in muscle-invasive bladder cancer. Clin. Cancer Res. 25, 977–988 (2019).
pubmed: 29980530
doi: 10.1158/1078-0432.CCR-18-1001
Wang, F., Dong, X., Yang, F. & Xing, N. Comparative analysis of differentially mutated genes in non-muscle and muscle-invasive bladder cancer in the Chinese population by whole exome sequencing. Front. Genet. 13, 831146 (2022).
pubmed: 35419031
pmcid: 8996331
doi: 10.3389/fgene.2022.831146
Maas, M., Todenhöfer, T. & Black, P. C. Urine biomarkers in bladder cancer — current status and future perspectives. Nat. Rev. Urol. 20, 597–614 (2023).
pubmed: 37225864
doi: 10.1038/s41585-023-00773-8
Kang, H. W. et al. Long-term validation of a molecular progression-associated gene classifier for prediction of muscle invasion in primary non-muscle-invasive bladder cancer. Oncol. Lett. 14, 2468–2474 (2017).
pubmed: 28781684
pmcid: 5530216
doi: 10.3892/ol.2017.6408
Kang, H. W. et al. Molecular progression risk score for prediction of muscle invasion in primary T1 high-grade bladder cancer. Clin. Genitourin. Cancer 16, 274–280 (2018).
pubmed: 29571585
doi: 10.1016/j.clgc.2018.02.001
Harvey, K. F., Zhang, X. & Thomas, D. M. The Hippo pathway and human cancer. Nat. Rev. Cancer 13, 246–257 (2013).
pubmed: 23467301
doi: 10.1038/nrc3458
Baek, S.-W. et al. YAP1 activation is associated with the progression and response to immunotherapy of non-muscle invasive bladder cancer. eBioMedicine 81, 104092 (2022).
pubmed: 35665684
pmcid: 9166372
doi: 10.1016/j.ebiom.2022.104092
Dyrskjot, L. et al. Analysis of molecular intra-patient variation and delineation of a prognostic 12-gene signature in non-muscle invasive bladder cancer; technology transfer from microarrays to PCR. Br. J. Cancer 107, 1392–1398 (2012).
pubmed: 22976798
pmcid: 3494423
doi: 10.1038/bjc.2012.412
Dyrskjot, L. et al. Prognostic impact of a 12-gene progression score in non-muscle-invasive bladder cancer: a prospective multicentre validation study. Eur. Urol. 72, 461–469 (2017).
pubmed: 28583312
doi: 10.1016/j.eururo.2017.05.040
Seiler, R. et al. Impact of molecular subtypes in muscle-invasive bladder cancer on predicting response and survival after neoadjuvant chemotherapy. Eur. Urol. 72, 544–554 (2017).
pubmed: 28390739
doi: 10.1016/j.eururo.2017.03.030
Robertson, A. G. et al. Comprehensive molecular characterization of muscle-invasive bladder cancer. Cell 171, 540–556 e25 (2017).
pubmed: 28988769
pmcid: 5687509
doi: 10.1016/j.cell.2017.09.007
Sjodahl, G. et al. A molecular taxonomy for urothelial carcinoma. Clin. Cancer Res. 18, 3377–3386 (2012).
pubmed: 22553347
doi: 10.1158/1078-0432.CCR-12-0077-T
Marzouka, N. A. et al. A validation and extended description of the Lund taxonomy for urothelial carcinoma using the TCGA cohort. Sci. Rep. 8, 3737 (2018).
pubmed: 29487377
pmcid: 5829240
doi: 10.1038/s41598-018-22126-x
Sjodahl, G., Eriksson, P., Liedberg, F. & Hoglund, M. Molecular classification of urothelial carcinoma: global mRNA classification versus tumour-cell phenotype classification. J. Pathol. 242, 113–125 (2017).
pubmed: 28195647
pmcid: 5413843
doi: 10.1002/path.4886
Marzouka, N. A. et al. The Lund molecular taxonomy applied to non-muscle-invasive urothelial carcinoma. J. Mol. Diagn. 24, 992–1008 (2022).
pubmed: 35853574
doi: 10.1016/j.jmoldx.2022.05.006
Aramendía Cotillas, E. et al. A versatile and upgraded version of the LundTax classification algorithm applied to independent cohorts. Preprint at bioRxiv https://doi.org/10.1101/2023.12.15.571519v1 (2023).
Hedegaard, J. et al. Comprehensive transcriptional analysis of early-stage urothelial carcinoma. Cancer Cell 30, 27–42 (2016).
pubmed: 27321955
doi: 10.1016/j.ccell.2016.05.004
Goel, A. et al. Combined exome and transcriptome sequencing of non-muscle-invasive bladder cancer: associations between genomic changes, expression subtypes, and clinical outcomes. Genome Med. 14, 59 (2022).
pubmed: 35655252
pmcid: 9164468
doi: 10.1186/s13073-022-01056-4
Erasmus Urology Research. IMPASSE-trial: improved patient stratification by molecular subtyping of high-risk non-muscle invasive bladder cancer and identification of novel treatments by ex vivo medium-throughput drug screening. Erasmus Urology Research https://www.erasmusurologyresearch.nl/impasse-trial/ (2024).
Meeks, J. J. et al. Genomic heterogeneity in bladder cancer: challenges and possible solutions to improve outcomes. Nat. Rev. Urol. 17, 259–270 (2020).
pubmed: 32235944
pmcid: 7968350
doi: 10.1038/s41585-020-0304-1
Lindskrog, S. V. et al. Single-nucleus and spatially resolved intratumor subtype heterogeneity in bladder cancer. Eur. Urol. Open Sci. 51, 78–88 (2023).
pubmed: 37187723
pmcid: 10175738
doi: 10.1016/j.euros.2023.03.006