Reprogramming of Nucleotide Metabolism Mediates Synergy between Epigenetic Therapy and MAP Kinase Inhibition.
Animals
Azetidines
/ pharmacology
Cell Cycle Checkpoints
/ drug effects
Cell Line, Tumor
Cell Proliferation
/ drug effects
Down-Regulation
/ drug effects
Drug Synergism
Epigenesis, Genetic
/ drug effects
Female
Gene Knockdown Techniques
HEK293 Cells
Humans
Mice, Inbred NOD
Mice, SCID
Mitogen-Activated Protein Kinase Kinases
/ antagonists & inhibitors
Mitogen-Activated Protein Kinases
/ antagonists & inhibitors
Neoplasm Proteins
/ metabolism
Nucleotides
/ metabolism
Ovarian Neoplasms
/ drug therapy
Piperidines
/ pharmacology
Protein Kinase Inhibitors
/ pharmacology
S Phase
/ drug effects
Xenograft Model Antitumor Assays
Journal
Molecular cancer therapeutics
ISSN: 1538-8514
Titre abrégé: Mol Cancer Ther
Pays: United States
ID NLM: 101132535
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
02
04
2020
revised:
31
07
2020
accepted:
08
10
2020
pubmed:
23
10
2020
medline:
13
8
2021
entrez:
22
10
2020
Statut:
ppublish
Résumé
Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare but often lethal cancer that is diagnosed at a median age of 24 years. Optimal management of patients is not well defined, and current treatment remains challenging, necessitating the discovery of novel therapeutic approaches. The identification of SMARCA4-inactivating mutations invariably characterizing this type of cancer provided insights facilitating diagnostic and therapeutic measures against this disease. We show here that the BET inhibitor OTX015 acts in synergy with the MEK inhibitor cobimetinib to repress the proliferation of SCCOHT
Identifiants
pubmed: 33087508
pii: 1535-7163.MCT-20-0259
doi: 10.1158/1535-7163.MCT-20-0259
doi:
Substances chimiques
Azetidines
0
Neoplasm Proteins
0
Nucleotides
0
Piperidines
0
Protein Kinase Inhibitors
0
Mitogen-Activated Protein Kinases
EC 2.7.11.24
Mitogen-Activated Protein Kinase Kinases
EC 2.7.12.2
cobimetinib
ER29L26N1X
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
64-75Subventions
Organisme : CIHR
ID : PJT-159759
Pays : Canada
Organisme : CIHR
ID : PJT-159663
Pays : Canada
Organisme : CIHR
ID : FDN-148390
Pays : Canada
Informations de copyright
©2020 American Association for Cancer Research.
Références
Clement PB. Selected miscellaneous ovarian lesions: small cell carcinomas, mesothelial lesions, mesenchymal and mixed neoplasms, and non-neoplastic lesions. Mod Pathol. 2005;18:S113–29.
Witkowski L, Goudie C, Ramos P, Boshari T, Brunet JS, Karnezis AN, et al. The influence of clinical and genetic factors on patient outcome in small cell carcinoma of the ovary, hypercalcemic type. Gynecol Oncol. 2016;141:454–60.
McCluggage WG, Oliva E, Connolly LE, McBride HA, Young RH. An immunohistochemical analysis of ovarian small cell carcinoma of hypercalcemic type. Int J Gynecol Pathol. 2004;23:330–6.
Witkowski L, Carrot-Zhang J, Albrecht S, Fahiminiya S, Hamel N, Tomiak E, et al. Germline and somatic SMARCA4 mutations characterize small cell carcinoma of the ovary, hypercalcemic type. Nat Genet. 2014;46:438–43.
Jelinic P, Mueller JJ, Olvera N, Dao F, Scott SN, Shah R, et al. Recurrent SMARCA4 mutations in small cell carcinoma of the ovary. Nat Genet. 2014;46:424–6.
Karnezis AN, Wang Y, Ramos P, Hendricks WP, Oliva E, D’Angelo E, et al. Dual loss of the SWI/SNF complex ATPases SMARCA4/BRG1 and SMARCA2/BRM is highly sensitive and specific for small cell carcinoma of the ovary, hypercalcaemic type. J Pathol. 2016;238:389–400.
Lu P, Roberts CW. The SWI/SNF tumor suppressor complex: regulation of promoter nucleosomes and beyond. Nucleus. 2013;4:374–8.
Shi J, Whyte WA, Zepeda-Mendoza CJ, Milazzo JP, Shen C, Roe JS, et al. Role of SWI/SNF in acute leukemia maintenance and enhancer-mediated Myc regulation. Genes Dev. 2013;27:2648–62.
Shorstova T, Marques M, Su J, Johnston J, Kleinman CL, Hamel N, et al. SWI/SNF-compromised cancers are susceptible to bromodomain inhibitors. Cancer Res. 2019;79:2761–74.
Kurimchak AM, Shelton C, Duncan KE, Johnson KJ, Brown J, O’Brien S, et al. Resistance to BET bromodomain inhibitors is mediated by kinome reprogramming in ovarian cancer. Cell Rep. 2016;16:1273–86.
Iniguez AB, Alexe G, Wang EJ, Roti G, Patel S, Chen L, et al. Resistance to epigenetic-targeted therapy engenders tumor cell vulnerabilities associated with enhancer remodeling. Cancer Cell. 2018;34:922–38.
Chua V, Orloff M, Teh JL, Sugase T, Liao C, Purwin TJ, et al. Stromal fibroblast growth factor 2 reduces the efficacy of bromodomain inhibitors in uveal melanoma. EMBO Mol Med. 2019;11:e9081.
Echevarria-Vargas IM, Reyes-Uribe PI, Guterres AN, Yin X, Kossenkov AV, Liu Q, et al. Co-targeting BET and MEK as salvage therapy for MAPK and checkpoint inhibitor-resistant melanoma. EMBO Mol Med. 2018;10:e8446.
2020.
Drissi R, Dubois ML, Douziech M, Boisvert FM. Quantitative proteomics reveals dynamic interactions of the minichromosome maintenance complex (MCM) in the cellular response to etoposide induced DNA damage. Mol Cell Proteomics. 2015;14:2002–13.
Hilmi K, Jangal M, Marques M, Zhao T, Saad A, Zhang C, et al. CTCF facilitates DNA double-strand break repair by enhancing homologous recombination repair. Sci Adv. 2017;3:e1601898.
Marques M, Beauchamp MC, Fleury H, Laskov I, Qiang S, Pelmus M, et al. Chemotherapy reduces PARP1 in cancers of the ovary: implications for future clinical trials involving PARP inhibitors. BMC Med. 2015;13:217.
Pena-Hernandez R, Marques M, Hilmi K, Zhao T, Saad A, Alaoui-Jamali MA, et al. Genome-wide targeting of the epigenetic regulatory protein CTCF to gene promoters by the transcription factor TFII-I. Proc Natl Acad Sci U S A. 2015;112:E677–86.
Bisikirska B, Bansal M, Shen Y, Teruya-Feldstein J, Chaganti R, Califano A. Elucidation and pharmacological targeting of novel molecular drivers of follicular lymphoma progression. Cancer Res. 2016;76:664–74.
Huang X, Yan J, Zhang M, Wang Y, Chen Y, Fu X, et al. Targeting epigenetic crosstalk as a therapeutic strategy for EZH2-aberrant solid tumors. Cell. 2018;175:186–99.
Adelmann CH, Truong KA, Liang RJ, Bansal V, Gandee L, Saporito RC, et al. MEK is a therapeutic and chemopreventative target in squamous cell carcinoma. J Invest Dermatol. 2016;136:1920–4.
Amorim S, Stathis A, Gleeson M, Iyengar S, Magarotto V, Leleu X, et al. Bromodomain inhibitor OTX015 in patients with lymphoma or multiple myeloma: a dose-escalation, open-label, pharmacokinetic, phase 1 study. Lancet Haematol. 2016;3:e196–204.
Rosen LS, LoRusso P, Ma WW, Goldman JW, Weise A, Colevas AD, et al. A first-in-human phase I study to evaluate the MEK1/2 inhibitor, cobimetinib, administered daily in patients with advanced solid tumors. Invest New Drugs. 2016;34:604–13.
Wilson PM, LaBonte MJ, Lenz HJ, Mack PC, Ladner RD. Inhibition of dUTPase induces synthetic lethality with thymidylate synthase-targeted therapies in non-small cell lung cancer. Mol Cancer Ther. 2012;11:616–28.
Zimling ZG, Santoni-Rugiu E, Bech C, Sorensen JB. High RRM1 expression is associated with adverse outcome in patients with cisplatin/vinorelbine-treated malignant pleural mesothelioma. Anticancer Res. 2015;35:6731–8.
Johnston PG, Lenz HJ, Leichman CG, Danenberg KD, Allegra CJ, Danenberg PV, et al. Thymidylate synthase gene and protein expression correlate and are associated with response to 5-fluorouracil in human colorectal and gastric tumors. Cancer Res. 1995;55:1407–12.
Ladner RD, Lynch FJ, Groshen S, Xiong YP, Sherrod A, Caradonna SJ, et al. dUTP nucleotidohydrolase isoform expression in normal and neoplastic tissues: association with survival and response to 5-fluorouracil in colorectal cancer. Cancer Res. 2000;60:3493–503.
Thymidylate synthase.
Akimov V, Barrio-Hernandez I, Hansen SVF, Hallenborg P, Pedersen AK, Bekker-Jensen DB, et al. UbiSite approach for comprehensive mapping of lysine and N-terminal ubiquitination sites. Nat Struct Mol Biol. 2018;25:631–40.
Berger FG, Berger SH. Thymidylate synthase as a chemotherapeutic drug target: where are we after fifty years?. Cancer Biol Ther. 2006;5:1238–41.
Friedkin M. Thymidylate synthetase. Adv Enzymol Relat Areas Mol Biol. 1973;38:235–92.
Carreras CW, Santi DV. The catalytic mechanism and structure of thymidylate synthase. Annu Rev Biochem. 1995;64:721–62.
Saviozzi S, Ceppi P, Novello S, Ghio P, Lo Iacono M, Borasio P, et al. Non-small cell lung cancer exhibits transcript overexpression of genes associated with homologous recombination and DNA replication pathways. Cancer Res. 2009;69:3390–6.
Zhao M, Tan B, Dai X, Shao Y, He Q, Yang B, et al. DHFR/TYMS are positive regulators of glioma cell growth and modulate chemo-sensitivity to temozolomide. Eur J Pharmacol. 2019;863:172665.
Takezawa K, Okamoto I, Okamoto W, Takeda M, Sakai K, Tsukioka S, et al. Thymidylate synthase as a determinant of pemetrexed sensitivity in non-small cell lung cancer. Br J Cancer. 2011;104:1594–601.
Gusella M, Frigo AC, Bolzonella C, Marinelli R, Barile C, Bononi A, et al. Predictors of survival and toxicity in patients on adjuvant therapy with 5-fluorouracil for colorectal cancer. Br J Cancer. 2009;100:1549–57.
Rees C, Beale P, Trigo JM, Mitchell F, Jackman A, Smith R, et al. Phase I trial of ZD9331, a nonpolyglutamatable thymidylate synthase inhibitor, given as a 5-day continuous infusion to patients with refractory solid malignancies. Clin Cancer Res. 2003;9:2049–55.
Wilson PM, Fazzone W, LaBonte MJ, Deng J, Neamati N, Ladner RD. Novel opportunities for thymidylate metabolism as a therapeutic target. Mol Cancer Ther. 2008;7:3029–37.
Fujita H, Ohuchida K, Mizumoto K, Itaba S, Ito T, Nakata K, et al. Gene expression levels as predictive markers of outcome in pancreatic cancer after gemcitabine-based adjuvant chemotherapy. Neoplasia. 2010;12:807–17.
Souglakos J, Boukovinas I, Taron M, Mendez P, Mavroudis D, Tripaki M, et al. Ribonucleotide reductase subunits M1 and M2 mRNA expression levels and clinical outcome of lung adenocarcinoma patients treated with docetaxel/gemcitabine. Br J Cancer. 2008;98:1710–5.
Marcotte R, Sayad A, Brown KR, Sanchez-Garcia F, Reimand J, Haider M, et al. Functional genomic landscape of human breast cancer drivers, vulnerabilities, and resistance. Cell. 2016;164:293–309.
Stratikopoulos EE, Dendy M, Szabolcs M, Khaykin AJ, Lefebvre C, Zhou MM, et al. Kinase and BET inhibitors together clamp inhibition of PI3K signaling and overcome resistance to therapy. Cancer Cell. 2015;27:837–51.
Berthon C, Raffoux E, Thomas X, Vey N, Gomez-Roca C, Yee K, et al. Bromodomain inhibitor OTX015 in patients with acute leukaemia: a dose-escalation, phase 1 study. Lancet Haematol. 2016;3:e186–95.
Lewin J, Soria JC, Stathis A, Delord JP, Peters S, Awada A, et al. Phase Ib trial with birabresib, a small-molecule inhibitor of bromodomain and extraterminal proteins, in patients with selected advanced solid tumors. J Clin Oncol. 2018;36:3007–14.
Yoshioka A, Tanaka S, Hiraoka O, Koyama Y, Hirota Y, Ayusawa D, et al. Deoxyribonucleoside triphosphate imbalance. 5-Fluorodeoxyuridine-induced DNA double strand breaks in mouse FM3A cells and the mechanism of cell death. J Biol Chem. 1987;262:8235–41.
Niida H, Katsuno Y, Sengoku M, Shimada M, Yukawa M, Ikura M, et al. Essential role of Tip60-dependent recruitment of ribonucleotide reductase at DNA damage sites in DNA repair during G1 phase. Genes Dev. 2010;24:333–8.
Havugimana PC, Hart GT, Nepusz T, Yang H, Turinsky AL, Li Z, et al. A census of human soluble protein complexes. Cell. 2012;150:1068–81.
.
.
Gilberto S, Peter M. Dynamic ubiquitin signaling in cell cycle regulation. J Cell Biol. 2017;216:2259–71.
Doi T, Yoh K, Shitara K, Takahashi H, Ueno M, Kobayashi S, et al. First-in-human phase 1 study of novel dUTPase inhibitor TAS-114 in combination with S-1 in Japanese patients with advanced solid tumors. Invest New Drugs. 2019;37:507–18.
Zou Y, Li W, Zhou J, Zhang J, Huang Y, Wang Z. ERK Inhibitor enhances everolimus efficacy through the attenuation of dNTP pools in renal cell carcinoma. Mol Ther Nucleic Acids. 2019;14:550–61.
Robinson AD, Eich ML, Varambally S. Dysregulation of de novo nucleotide biosynthetic pathway enzymes in cancer and targeting opportunities. Cancer Lett. 2020;470:134–40.
Nathanson DA, Armijo AL, Tom M, Li Z, Dimitrova E, Austin WR, et al. Co-targeting of convergent nucleotide biosynthetic pathways for leukemia eradication. J Exp Med. 2014;211:473–86.