Epigenetic modulations in cancer: predictive biomarkers and potential targets for overcoming the resistance to topoisomerase I inhibitors

References

• Mognato M, Burdak-Rothkamm S, Rothkamm K. Interplay between DNA replication stress, chromatin dynamics and DNA-damage response for the maintenance of genome stability. Mutat Res Rev Mutat Res. 2021;787:1.
   Web of Science ®Google Scholar
• Peschansky VJ, Wahlestedt C. Non-coding RNAs as direct and indirect modulators of epigenetic regulation. Epigenetics. 2014;9(1):3–16.
   PubMed Web of Science ®Google Scholar
• Miller JL, Grant PA. The role of DNA methylation and histone modifications in transcriptional regulation in humans. Subcell Biochem. 2013;61:289–317.
   PubMedGoogle Scholar
• Jin B, Li Y, Robertson KD. DNA methylation: superior or subordinate in the epigenetic hierarchy? Genes Cancer. 2011;2(6):607–617.
   PubMedGoogle Scholar
• Das J, Chandra L, Gandhi G, et al. Evaluation of promoter hypermethylation of tumor suppressor gene BRCA1 in epithelial ovarian cancer. J Cancer Res Ther. 2022;18(6):1578–1582.
   PubMed Web of Science ®Google Scholar
• Bai X, Fu Y, Xue H, et al. BRCA1 promoter hypermethylation in sporadic epithelial ovarian carcinoma: association with low expression of BRCA1, improved survival and co-expression of DNA methyltransferases. Oncol Lett. 2014;7(4):1088–1096.
   PubMed Web of Science ®Google Scholar
• Shimizu R, Muto T, Aoyama K, et al. Possible role of intragenic DNA hypermethylation in gene silencing of the tumor suppressor gene NR4A3 in acute myeloid leukemia. Leuk Res. 2016;50:85–94.
   PubMed Web of Science ®Google Scholar
• Kao CC, Chang YL, Liu HY, et al. DNA hypomethylation is associated with the overexpression of INHBA in upper tract urothelial carcinoma. Int J Mol Sci. 2022;23(4):2072.
   Web of Science ®Google Scholar
• Nishiyama A, Nakanishi M. Navigating the DNA methylation landscape of cancer. Trends Genet. 2021;37(11):1012–1027.
   PubMed Web of Science ®Google Scholar
• Recillas-Targa F. Cancer epigenetics: an overview. Arch Med Res. 2022;53(8):732–740.
   PubMed Web of Science ®Google Scholar
• Gomes AQ, Nolasco S, Soares H. Non-coding RNAs: multi-tasking molecules in the cell. Int J Mol Sci. 2013;14(8):16010–16039.
   PubMed Web of Science ®Google Scholar
• Bukowski K, Kciuk M, Kontek R. Mechanisms of multidrug resistance in cancer chemotherapy. Int J Mol Sci. 2020;21(9):3233.
   Web of Science ®Google Scholar
• Lu Y, Chan YT, Tan HY, et al. Epigenetic regulation in human cancer: the potential role of epi-drug in cancer therapy. Mol Cancer. 2020;19(1):79.
   PubMed Web of Science ®Google Scholar
• Oberstadt MC, Bien-Möller S, Weitmann K, et al. Epigenetic modulation of the drug resistance genes MGMT, ABCB1 and ABCG2 in glioblastoma multiforme. BMC Cancer. 2013;13:617.
   PubMed Web of Science ®Google Scholar
• Zappe K, Cichna-Markl M. Aberrant DNA methylation of ABC transporters in cancer. Cells. 2020;9(10):2281.
   PubMed Web of Science ®Google Scholar
• Karakaidos P, Karagiannis D, Rampias T. Resolving DNA damage: epigenetic regulation of DNA repair. Molecules. 2020;25(11):2496.
   PubMed Web of Science ®Google Scholar
• Fernandez A, O'Leary C, O'Byrne KJ, et al. Epigenetic mechanisms in DNA double strand break repair: a clinical review. Front Mol Biosci. 2021;8:685440.
   PubMed Web of Science ®Google Scholar
• Gao D, Herman JG, Guo M. The clinical value of aberrant epigenetic changes of DNA damage repair genes in human cancer. Oncotarget. 2016;7(24):37331–37346.
   PubMedGoogle Scholar
• Champoux JJ. DNA topoisomerases: structure, function, and mechanism. Annu Rev Biochem. 2001;70:369–413.
   PubMed Web of Science ®Google Scholar
• Chen SH, Chan NL, Hsieh TS. New mechanistic and functional insights into DNA topoisomerases. Annu Rev Biochem. 2013;82:139–170.
   PubMed Web of Science ®Google Scholar
• Corbett KD, Berger JM. Structure, molecular mechanisms, and evolutionary relationships in DNA topoisomerases. Annu Rev Biophys Biomol Struct. 2004;33:95–118.
   PubMedGoogle Scholar
• Nitiss JL. DNA topoisomerase II and its growing repertoire of biological functions. Nat Rev Cancer. 2009;9(5):327–337.
   PubMed Web of Science ®Google Scholar
• Pommier Y, Sun Y, Huang SN, et al. Roles of eukaryotic topoisomerases in transcription, replication and genomic stability. Nat Rev Mol Cell Biol. 2016;17(11):703–721.
   PubMed Web of Science ®Google Scholar
• Vos SM, Tretter EM, Schmidt BH, et al. All tangled up: how cells direct, manage and exploit topoisomerase function. Nat Rev Mol Cell Biol. 2011;12(12):827–841.
   PubMed Web of Science ®Google Scholar
• Delgado JL, Hsieh CM, Chan NL, et al. Topoisomerases as anticancer targets. Biochem J. 2018;475(2):373–398.
   PubMedGoogle Scholar
• Martino E, Della Volpe S, Terribile E, et al. The long story of camptothecin: from traditional medicine to drugs. Bioorg Med Chem Lett. 2017;27(4):701–707.
   PubMed Web of Science ®Google Scholar
• Nitiss JL. Targeting DNA topoisomerase II in cancer chemotherapy. Nat Rev Cancer. 2009 May;9(5):338–350.
   PubMed Web of Science ®Google Scholar
• Pommier Y. Drugging topoisomerases: lessons and challenges. ACS Chem Biol. 2013;8(1):82–95.
   PubMed Web of Science ®Google Scholar
• Pommier Y, Kiselev E, Marchand C. Interfacial inhibitors. Bioorg Med Chem Lett. 2015;25(18):3961–3965.
   PubMed Web of Science ®Google Scholar
• Arakawa H, Iguchi T, Morita M, et al. Novel indolocarbazole compound 6-N-formylamino-12,13-dihydro-1,11-dihydroxy- 13-(beta-D-glucopyranosyl)-5H-indolo[2,3-a]pyrrolo-[3,4-c]carbazole- 5,7(6H)-dione (NB-506): its potent antitumor activities in mice. Cancer Res. 1995;55(6):1316–1320.
   PubMed Web of Science ®Google Scholar
• Molinaro C, Wambang N, Bousquet T, et al. A novel copper(II) indenoisoquinoline complex inhibits topoisomerase I, induces G2 phase arrest, and autophagy in three adenocarcinomas. Front Oncol. 2022;12:837373.
   PubMed Web of Science ®Google Scholar
• Teicher BA. Next generation topoisomerase I inhibitors: rationale and biomarker strategies. Biochem Pharmacol. 2008;75(6):1262–1271.
   PubMed Web of Science ®Google Scholar
• Thomas A, Pommier Y. Targeting topoisomerase I in the era of precision medicine. Clin Cancer Res. 2019;25(22):6581–6589.
   PubMed Web of Science ®Google Scholar
• Kavanagh JJ, Verschraegen CF, Kudelka AP. Irinotecan in cervical cancer. Oncology. 1998;12(8 Suppl 6):94–98.
   PubMed Web of Science ®Google Scholar
• Fujita K, Kubota Y, Ishida H, et al. Irinotecan, a key chemotherapeutic drug for metastatic colorectal cancer. World J Gastroenterol. 2015;21(43):12234–12248.
   PubMed Web of Science ®Google Scholar
• Treat J, Huang CH, Lane SR, et al. Topotecan in the treatment of relapsed small cell lung cancer patients with poor performance status. Oncologist. 2004;9(2):173–181.
   PubMed Web of Science ®Google Scholar
• O'Reilly S. Topotecan: what dose, what schedule, what route? Clin Cancer Res. 1999;5(1):3–5.
   PubMed Web of Science ®Google Scholar
• Coronel J, Cetina L, Candelaria M, et al. Weekly topotecan as second- or third-line treatment in patients with recurrent or metastatic cervical cancer. Med Oncol. 2009;26(2):210–214.
   PubMed Web of Science ®Google Scholar
• Yu Q, Chen Y, Yang H, et al. The antitumor activity of CYB-L10, a human topoisomerase IB catalytic inhibitor. J Enzyme Inhib Med Chem. 2019;34(1):818–822.
   PubMed Web of Science ®Google Scholar
• Ganguly A, Das B, Roy A, et al. Betulinic acid, a catalytic inhibitor of topoisomerase I, inhibits reactive oxygen species-mediated apoptotic topoisomerase I-DNA cleavable complex formation in prostate cancer cells but does not affect the process of cell death. Cancer Res. 2007;67(24):11848–11858.
   PubMed Web of Science ®Google Scholar
• Van Cutsem E, Cervantes A, Nordlinger B, et al. Metastatic colorectal cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014;25(Suppl 3):iii1–9.
   PubMed Web of Science ®Google Scholar
• Kumar L, Harish P, Malik PS, et al. Chemotherapy and targeted therapy in the management of cervical cancer. Curr Probl Cancer. 2018;42(2):120–128.
   PubMed Web of Science ®Google Scholar
• Marth C, Landoni F, Mahner S, et al. Cervical cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017;28(suppl_4):iv72–iv83.
   PubMed Web of Science ®Google Scholar
• Beretta GL, Perego P, Zunino F. Targeting topoisomerase I: molecular mechanisms and cellular determinants of response to topoisomerase I inhibitors. Expert Opin Ther Targets. 2008;12(10):1243–1256.
   PubMed Web of Science ®Google Scholar
• Tagen M, Zhuang Y, Zhang F, et al. P-glycoprotein, but not multidrug resistance protein 4, plays a role in the systemic clearance of irinotecan and SN-38 in mice. Drug Metab Lett. 2010;4(4):195–201.
   PubMedGoogle Scholar
• Tian Q, Zhang J, Chan SY, et al. Topotecan is a substrate for multidrug resistance associated protein 4. Curr Drug Metab. 2006;7(1):105–118.
   PubMed Web of Science ®Google Scholar
• Alagoz M, Gilbert DC, El-Khamisy S, et al. DNA repair and resistance to topoisomerase I inhibitors: mechanisms, biomarkers and therapeutic targets. Curr Med Chem. 2012;19(23):3874–3885.
   PubMed Web of Science ®Google Scholar
• Pommier Y, Pourquier P, Urasaki Y, et al. Topoisomerase I inhibitors: selectivity and cellular resistance. Drug Resist Updat. 1999;2(5):307–318.
   PubMed Web of Science ®Google Scholar
• Li M, Liu Y. Topoisomerase I in human disease pathogenesis and treatments. Genomics Proteomics Bioinformatics. 2016;14(3):166–171.
   PubMed Web of Science ®Google Scholar
• Burgess DJ, Doles J, Zender L, et al. Topoisomerase levels determine chemotherapy response in vitro and in vivo. Proc Natl Acad Sci U S A. 2008;105(26):9053–9058.
   PubMed Web of Science ®Google Scholar
• Bandyopadhyay K, Gjerset RA. Protein kinase CK2 is a Central regulator of topoisomerase I hyperphosphorylation and camptothecin sensitivity in cancer cell lines. Biochemistry. 2011;50(5):704–714.
   PubMed Web of Science ®Google Scholar
• Beretta GL, Gatti L, Perego P, et al. Camptothecin resistance in cancer: insights into the molecular mechanisms of a DNA-damaging drug. Curr Med Chem. 2013;20(12):1541–1565.
   PubMed Web of Science ®Google Scholar
• Horie K, Tomida A, Sugimoto Y, et al. SUMO-1 conjugation to intact DNA topoisomerase I amplifies cleavable complex formation induced by camptothecin. Oncogene. 2002;21(52):7913–7922.
   PubMed Web of Science ®Google Scholar
• Moukharskaya J, Verschraegen C. Topoisomerase 1 inhibitors and cancer therapy. Hematol Oncol Clin North Am. 2012;26(3):507–525, vii.
   PubMed Web of Science ®Google Scholar
• Li F, Jiang T, Li Q, et al. Camptothecin (CPT) and its derivatives are known to target topoisomerase I (Top1) as their mechanism of action: did we miss something in CPT analogue molecular targets for treating human disease such as cancer? Am J Cancer Res. 2017;7(12):2350–2394.
   PubMed Web of Science ®Google Scholar
• Ando K, Shah AK, Sachdev V, et al. Camptothecin resistance is determined by the regulation of topoisomerase I degradation mediated by ubiquitin proteasome pathway. Oncotarget. 2017;8(27):43733–43751.
   PubMedGoogle Scholar
• Hertzberg RP, Caranfa MJ, Holden KG, et al. Modification of the hydroxy lactone ring of camptothecin: inhibition of mammalian topoisomerase I and biological activity. J Med Chem. 1989;32(3):715–720.
   PubMed Web of Science ®Google Scholar
• Burke TG, Xiang T-X, Anderson BD, et al. Recent advances in camptothecin drug design and delivery strategies. In: Adams VR, Burke TG, editors. Camptothecins in cancer therapy. Totowa (NJ): humana Press; 2005. p. 171–190.
   Google Scholar
• Zou J, Li S, Chen Z, et al. A novel oral camptothecin analog, gimatecan, exhibits superior antitumor efficacy than irinotecan toward esophageal squamous cell carcinoma in vitro and in vivo. Cell Death Dis. 2018;9(6):661.
   PubMed Web of Science ®Google Scholar
• Talukdar A, Kundu B, Sarkar D, et al. Topoisomerase I inhibitors: challenges, progress and the road ahead. Eur J Med Chem. 2022;236:114304.
   PubMed Web of Science ®Google Scholar
• Lopez-Baena M, Mateos S, Pinero J, et al. Enhanced sensitivity to topoisomerase inhibitors in synchronous CHO cells pre-treated with 5-azacytidine. Mutat Res. 1998;421(1):109–116.
   PubMed Web of Science ®Google Scholar
• Crea F, Giovannetti E, Cortesi F, et al. Epigenetic mechanisms of irinotecan sensitivity in colorectal cancer cell lines. Mol Cancer Ther. 2009;8(7):1964–1973.
   PubMed Web of Science ®Google Scholar
• Zhao R, Choi BY, Lee MH, et al. Implications of genetic and epigenetic alterations of CDKN2A (p16(INK4a)) in cancer. EBioMedicine. 2016;8:30–39.
   PubMed Web of Science ®Google Scholar
• Sharma A, Vatapalli R, Abdelfatah E, et al. Hypomethylating agents synergize with irinotecan to improve response to chemotherapy in colorectal cancer cells. PLoS One. 2017;12(4):e0176139.
   PubMed Web of Science ®Google Scholar
• Sharma A, Vatapalli R, Abdelfatah E, et al. Correction: hypomethylating agents synergize with irinotecan to improve response to chemotherapy in colorectal cancer cells. PLoS One. 2020;15(11):e0242750.
   PubMed Web of Science ®Google Scholar
• Powers JF, Korgaonkar PG, Fliedner S, et al. Cytocidal activities of topoisomerase 1 inhibitors and 5-azacytidine against pheochromocytoma/paraganglioma cells in primary human tumor cultures and mouse cell lines. PLoS One. 2014;9(2):e87807.
   PubMed Web of Science ®Google Scholar
• Hakata S, Terashima J, Shimoyama Y, et al. Differential sensitization of two human colon cancer cell lines to the antitumor effects of irinotecan combined with 5-aza-2'-deoxycytidine. Oncol Lett. 2018;15(4):4641–4648.
   PubMed Web of Science ®Google Scholar
• Christman JK. 5-Azacytidine and 5-aza-2'-deoxycytidine as inhibitors of DNA methylation: mechanistic studies and their implications for cancer therapy. Oncogene. 2002;21(35):5483–5495.
   PubMed Web of Science ®Google Scholar
• Ohmori T, Podack ER, Nishio K, et al. Apoptosis of lung cancer cells caused by some anti-cancer agents (MMC, CPT-11, ADM) is inhibited by bcl-2. Biochem Biophys Res Commun. 1993;192(1):30–36.
   PubMed Web of Science ®Google Scholar
• Palissot V, Belhoussine R, Carpentier Y, et al. Resistance to apoptosis induced by topoisomerase I inhibitors in multidrug-resistant HL60 leukemic cells. Biochem Biophys Res Commun. 1998;245(3):918–922.
   PubMed Web of Science ®Google Scholar
• Moro H, Hattori N, Nakamura Y, et al. Epigenetic priming sensitizes gastric cancer cells to irinotecan and cisplatin by restoring multiple pathways. Gastric Cancer. 2020;23(1):105–115.
   PubMed Web of Science ®Google Scholar
• Moro H, Hattori N, Nakamura Y, et al. Correction to: Epigenetic priming sensitizes gastric cancer cells to irinotecan and cisplatin by restoring multiple pathways. Gastric Cancer. 2020;23(1):116–117.
   PubMed Web of Science ®Google Scholar
• Ding L, Qiu L, Zhang J, et al. Camptothecin-induced cell proliferation inhibition and apoptosis enhanced by DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine. Biol Pharm Bull. 2009;32(6):1105–1108.
   PubMed Web of Science ®Google Scholar
• Orta ML, Mateos S, Cortes F. DNA demethylation protects from cleavable complex stabilization and DNA strand breakage induced by the topoisomerase type I inhibitor camptothecin. Mutagenesis. 2009 May;24(3):237–244.
   PubMed Web of Science ®Google Scholar
• Gagnon JF, Bernard O, Villeneuve L, et al. Irinotecan inactivation is modulated by epigenetic silencing of UGT1A1 in Colon cancer. Clin Cancer Res. 2006;12(6):1850–1858.
   PubMed Web of Science ®Google Scholar
• Masuda K, Banno K, Yanokura M, et al. Association of epigenetic inactivation of the WRN gene with anticancer drug sensitivity in cervical cancer cells. Oncol Rep. 2012;28(4):1146–1152.
   PubMed Web of Science ®Google Scholar
• Miyaki Y, Suzuki K, Koizumi K, et al. Identification of a potent epigenetic biomarker for resistance to camptothecin and poor outcome to irinotecan-based chemotherapy in Colon cancer. Int J Oncol. 2012;40(1):217–226.
   PubMed Web of Science ®Google Scholar
• Li Y, Seto E. HDACs and HDAC inhibitors in cancer development and therapy. Cold Spring Harb Perspect Med. 2016;6(10):a026831.
   PubMed Web of Science ®Google Scholar
• Wu D, Qiu Y, Jiao Y, et al. Small molecules targeting HATs, HDACs, and BRDs in cancer therapy [review]. Front Oncol. 2020;10:560487.
   PubMedGoogle Scholar
• Sarcar B, Kahali S, Chinnaiyan P. Vorinostat enhances the cytotoxic effects of the topoisomerase I inhibitor SN38 in glioblastoma cell lines. J Neurooncol. 2010;99(2):201–207.
   PubMed Web of Science ®Google Scholar
• Bruzzese F, Rocco M, Castelli S, et al. Synergistic antitumor effect between vorinostat and topotecan in small cell lung cancer cells is mediated by generation of reactive oxygen species and DNA damage-induced apoptosis. Mol Cancer Ther. 2009;8(11):3075–3087.
   PubMed Web of Science ®Google Scholar
• Gray J, Cubitt CL, Zhang S, et al. Combination of HDAC and topoisomerase inhibitors in small cell lung cancer. Cancer Biol Ther. 2012;13(8):614–622.
   PubMed Web of Science ®Google Scholar
• Wasim L, Chopra M. Panobinostat induces apoptosis via production of reactive oxygen species and synergizes with topoisomerase inhibitors in cervical cancer cells. Biomed Pharmacother. 2016;84:1393–1405.
   PubMed Web of Science ®Google Scholar
• Wasim L, Chopra M. Synergistic anticancer effect of panobinostat and topoisomerase inhibitors through ROS generation and intrinsic apoptotic pathway induction in cervical cancer cells. Cell Oncol. 2018;41(2):201–212.
   PubMed Web of Science ®Google Scholar
• Daud AI, Dawson J, DeConti RC, et al. Potentiation of a topoisomerase I inhibitor, karenitecin, by the histone deacetylase inhibitor valproic acid in melanoma: translational and phase I/II clinical trial. Clin Cancer Res. 2009;15(7):2479–2487.
   PubMed Web of Science ®Google Scholar
• Meisenberg C, Ashour ME, El-Shafie L, et al. Epigenetic changes in histone acetylation underpin resistance to the topoisomerase I inhibitor irinotecan. Nucleic Acids Res. 2017;45(3):1159–1176.
   PubMed Web of Science ®Google Scholar
• Wang L, Chan CEL, Wong AL, et al. Combined use of irinotecan with histone deacetylase inhibitor belinostat could cause severe toxicity by inhibiting SN-38 glucuronidation via UGT1A1. Oncotarget. 2017;8(25): 41572–41581.
   PubMedGoogle Scholar
• Guerrant W, Patil V, Canzoneri JC, et al. Dual-acting histone deacetylase-topoisomerase I inhibitors. Bioorg Med Chem Lett. 2013;23(11):3283–3287.
   PubMed Web of Science ®Google Scholar
• Seo YH. Dual inhibitors against topoisomerases and histone deacetylases. J Cancer Prev. 2015;20(2):85–91.
   PubMedGoogle Scholar
• Cincinelli R, Musso L, Artali R, et al. Hybrid topoisomerase I and HDAC inhibitors as dual action anticancer agents. PLoS One. 2018;13(10):e0205018.
   PubMed Web of Science ®Google Scholar
• Cincinelli R, Musso L, Artali R, et al. Camptothecin-psammaplin a hybrids as topoisomerase I and HDAC dual-action inhibitors. Eur J Med Chem. 2018;143:2005–2014.
   PubMed Web of Science ®Google Scholar
• Ma H, Li L, Gai Y, et al. Histone acetyltransferases and deacetylases are required for virulence, conidiation, DNA damage repair, and multiple stresses resistance of Alternaria alternata. Front Microbiol. 2021;12:783633.
   PubMed Web of Science ®Google Scholar
• Yang X, Li L, Liang J, et al. Histone acetyltransferase 1 promotes homologous recombination in DNA repair by facilitating histone turnover. J Biol Chem. 2013;288(25):18271–18282.
   PubMed Web of Science ®Google Scholar
• Kolonko EM, Albaugh BN, Lindner SE, et al. Catalytic activation of histone acetyltransferase Rtt109 by a histone chaperone. Proc Natl Acad Sci USA. 2010;107(47):20275–20280.
   PubMed Web of Science ®Google Scholar
• Kwon S, Lee J, Jeon J, et al. Role of the histone acetyltransferase Rtt109 in development and pathogenicity of the rice blast fungus. Mol Plant Microbe Interact. 2018;31(11):1200–1210.
   PubMed Web of Science ®Google Scholar
• Han J, Zhou H, Horazdovsky B, et al. Rtt109 acetylates histone H3 lysine 56 and functions in DNA replication. Science. 2007;315(5812):653–655.
   PubMed Web of Science ®Google Scholar
• Wang X, Chang P, Ding J, ewt al. Distinct and redundant roles of the two MYST histone acetyltransferases Esa1 and Sas2 in cell growth and morphogenesis of Candida albicans. Eukaryot Cell. 2013;12(3):438–449.
   PubMedGoogle Scholar
• Noguchi C, Singh T, Ziegler MA, et al. The NuA4 acetyltransferase and histone H4 acetylation promote replication recovery after topoisomerase I-poisoning. Epigenetics Chromatin. 2019;12(1):24.
   PubMedGoogle Scholar
• Bird AW, Yu DY, Pray-Grant MG, et al. Acetylation of histone H4 by Esa1 is required for DNA double-strand break repair. Nature. 2002;419(6905):411–415.
   PubMed Web of Science ®Google Scholar
• Bandyopadhyay K, Baneres JL, Martin A, et al. Spermidinyl-CoA-based HAT inhibitors block DNA repair and provide cancer-specific chemo- and radiosensitization. Cell Cycle. 2009;8(17):2779–2788.
   PubMed Web of Science ®Google Scholar
• Kaur G, Reinhart RA, Monks A, et al. Bromodomain and hedgehog pathway targets in small cell lung cancer. Cancer Lett. 2016;371(2):225–239.
   PubMed Web of Science ®Google Scholar
• Lee SY, Kim JJ, Miller KM. Bromodomain proteins: protectors against endogenous DNA damage and facilitators of genome integrity. Exp Mol Med. 2021;53(9):1268–1277.
   PubMed Web of Science ®Google Scholar
• Lei L, Xie X, He L, et al. The bromodomain and extra-terminal domain inhibitor JQ1 synergistically sensitizes human colorectal cancer cells to topoisomerase I inhibitors through repression of Mre11-mediated DNA repair pathway. Invest New Drugs. 2021;39(2):362–376.
   PubMed Web of Science ®Google Scholar
• Kim JJ, Lee SY, Gong F, et al. Systematic bromodomain protein screens identify homologous recombination and R-loop suppression pathways involved in genome integrity. Genes Dev. 2019;33(23–24):1751–1774.
   PubMed Web of Science ®Google Scholar
• Li X, Baek G, Carreira S, et al. Targeting radioresistance and replication fork stability in prostate cancer. JCI Insight. 2022;7(9):e152955.
   PubMed Web of Science ®Google Scholar
• Berenguer-Daizé C, Astorgues-Xerri L, Odore E, et al. OTX015 (MK-8628), a novel BET inhibitor, displays in vitro and in vivo antitumor effects alone and in combination with conventional therapies in glioblastoma models. Int J Cancer. 2016;139(9):2047–2055.
   PubMed Web of Science ®Google Scholar
• Peng H, Zhang S, Peng Y, et al. Yeast bromodomain factor 1 and its human homolog TAF1 play conserved roles in promoting homologous recombination. Adv Sci. 2021;8(15):e2100753.
   Web of Science ®Google Scholar
• Garabedian MV, Noguchi C, Ziegler MA, et al. The double-bromodomain proteins Bdf1 and Bdf2 modulate chromatin structure to regulate S-phase stress response in Schizosaccharomyces pombe. Genetics. 2012;190(2):487–500.
   PubMed Web of Science ®Google Scholar
• Greer EL, Shi Y. Histone methylation: a dynamic mark in health, disease and inheritance. Nat Rev Genet. 2012;13(5):343–357.
   PubMed Web of Science ®Google Scholar
• Song Y, Wu F, Wu J. Targeting histone methylation for cancer therapy: enzymes, inhibitors, biological activity and perspectives. J Hematol Oncol. 2016;9(1):49.
   PubMedGoogle Scholar
• Sterling J, Menezes SV, Abbassi RH, et al. Histone lysine demethylases and their functions in cancer. Int J Cancer. 2021;148(10):2375–2388. Oct 31.
   PubMed Web of Science ®Google Scholar
• Singh S, Abu-Zaid A, Lin W, et al. 17-DMAG dually inhibits Hsp90 and histone lysine demethylases in alveolar rhabdomyosarcoma. iScience. 2021;24(1):101996.
   PubMed Web of Science ®Google Scholar
• Oki S, Sone K, Oda K, et al. Oncogenic histone methyltransferase EZH2: a novel prognostic marker with therapeutic potential in endometrial cancer. Oncotarget. 2017;8(25):40402–40411.
   PubMedGoogle Scholar
• Li T, Yu C, Zhuang S. Histone methyltransferase EZH2: a potential therapeutic target for kidney diseases. Front Physiol. 2021;12:640700.
   PubMed Web of Science ®Google Scholar
• Wu C, Jin X, Yang J, et al. Inhibition of EZH2 by chemo- and radiotherapy agents and small molecule inhibitors induces cell death in castration-resistant prostate cancer. Oncotarget. 2016;7(3):3440–3452.
   PubMedGoogle Scholar
• Kurmasheva RT, Erickson SW, Earley E, et al. In vivo evaluation of the EZH2 inhibitor (EPZ011989) alone or in combination with standard of care cytotoxic agents against pediatric malignant rhabdoid tumor preclinical models-A report from the pediatric preclinical testing consortium. Pediatr Blood Cancer. 2021;68(2):e28772.
   PubMed Web of Science ®Google Scholar
• Slack FJ, Chinnaiyan AM. The role of non-coding RNAs in oncology. Cell. 2019;179(5):1033–1055.
   PubMed Web of Science ®Google Scholar
• Kwon J, Jo YJ, Namgoong S, et al. Functional roles of hnRNPA2/B1 regulated by METTL3 in mammalian embryonic development. Sci Rep. 2019;9(1):8640.
   PubMedGoogle Scholar
• Kaikkonen MU, Lam MT, Glass CK. Non-coding RNAs as regulators of gene expression and epigenetics. Cardiovasc Res. 2011;90(3):430–440.
   PubMed Web of Science ®Google Scholar
• Ponting CP, Oliver PL, Reik W. Evolution and functions of long noncoding RNAs. Cell. 2009;136(4):629–641.
   PubMed Web of Science ®Google Scholar
• Sun YM, Chen YQ. Principles and innovative technologies for decrypting noncoding RNAs: from discovery and functional prediction to clinical application. J Hematol Oncol. 2020;13(1):109.
   PubMed Web of Science ®Google Scholar
• Saliminejad K, Khorram Khorshid HR, Soleymani Fard S, et al. An overview of microRNAs: biology, functions, therapeutics, and analysis methods. J Cell Physiol. 2019 May;234(5):5451–5465.
   PubMed Web of Science ®Google Scholar
• Macfarlane LA, Murphy PR. MicroRNA: biogenesis, function and role in cancer. Curr Genomics. 2010;11(7):537–561.
   PubMed Web of Science ®Google Scholar
• Wang N, Zhu M, Tsao SW, et al. MiR-23a-mediated inhibition of topoisomerase 1 expression potentiates cell response to etoposide in human hepatocellular carcinoma. Mol Cancer. 2013;12(1):119.
   PubMed Web of Science ®Google Scholar
• Zhang P, Yin J, Yuan L, et al. MicroRNA-139 suppresses hepatocellular carcinoma cell proliferation and migration by directly targeting topoisomerase I. Oncol Lett. 2019;17(2):1903–1913.
   PubMed Web of Science ®Google Scholar
• To KK, Leung WW, Ng SS. Exploiting a novel miR-519c-HuR-ABCG2 regulatory pathway to overcome chemoresistance in colorectal cancer. Exp Cell Res. 2015;338(2):222–231.
   PubMed Web of Science ®Google Scholar
• Chen SM, Chou WC, Hu LY, et al. The effect of MicroRNA-124 overexpression on anti-Tumor drug sensitivity. PLoS One. 2015;10(6):e0128472.
   PubMed Web of Science ®Google Scholar
• Munschauer M, Nguyen CT, Sirokman K, et al. The NORAD lncRNA assembles a topoisomerase complex critical for genome stability. Nature. 2018;561(7721):132–136.
   PubMed Web of Science ®Google Scholar
• Munschauer M, Nguyen CT, Sirokman K, et al. Publisher correction: the NORAD lncRNA assembles a topoisomerase complex critical for genome stability. Nature. 2018;563(7733):E32.
   PubMedGoogle Scholar
• Statello L, Ali MM, Reischl S, et al. The DNA damage inducible lncRNA SCAT7 regulates genomic integrity and topoisomerase 1 turnover in lung adenocarcinoma. NAR Cancer. 2021;3(1):zcab002.
   PubMedGoogle Scholar
• Zhou X, Liu S, Cai G, et al. Long non coding RNA MALAT1 promotes tumor growth and metastasis by inducing epithelial-mesenchymal transition in oral squamous cell carcinoma. Sci Rep. 2015;5:15972.
   PubMed Web of Science ®Google Scholar
• Gong WJ, Yin JY, Li XP, et al. Association of well-characterized lung cancer lncRNA polymorphisms with lung cancer susceptibility and platinum-based chemotherapy response. Tumour Biol. 2016;37(6):8349–8358.
   PubMedGoogle Scholar
• Lampropoulou DI, Aravantinos G, Katifelis H, et al. Long non-coding RNA polymorphisms and prediction of response to chemotherapy based on irinotecan in patients with metastatic colorectal cancer. Cancer Biomark. 2019;25(2):213–221.
   PubMed Web of Science ®Google Scholar
• Sun F, Liang W, Qian J. The identification of CRNDE, H19, UCA1 and HOTAIR as the key lncRNAs involved in oxaliplatin or irinotecan resistance in the chemotherapy of colorectal cancer based on integrative bioinformatics analysis. Mol Med Rep. 2019;20(4):3583–3596.
   PubMed Web of Science ®Google Scholar
• Ayoub NM. Editorial: novel combination therapies for the treatment of solid cancers. Front Oncol. 2021;11:708943.
   PubMed Web of Science ®Google Scholar
• Bayat Mokhtari R, Homayouni TS, Baluch N, et al. Combination therapy in combating cancer. Oncotarget. 2017;8(23):38022–38043.
   PubMed Web of Science ®Google Scholar
• Candelaria M, Gallardo-Rincon D, Arce C, et al. A phase II study of epigenetic therapy with hydralazine and magnesium valproate to overcome chemotherapy resistance in refractory solid tumors. Ann Oncol. 2007;18(9):1529–1538.
   PubMed Web of Science ®Google Scholar
• A phase II study of epigenetic therapy to overcome chemotherapy resistance in refractory solid tumors. https://ClinicalTrials.gov/show/NCT00404508.
   Google Scholar
• Lee V, Wang J, Zahurak M, et al. A phase I trial of a guadecitabine (SGI-110) and irinotecan in metastatic colorectal cancer patients previously exposed to irinotecan. Clin Cancer Res. 2018;24(24):6160–6167.
   PubMed Web of Science ®Google Scholar
• Phase I/II study of SGI-110 with irinotecan versus regorafenib or TAS-102 in metastatic colorectal cancer. https://ClinicalTrials.gov/show/NCT01896856.
   Google Scholar
• Phase I/II trial of valproic acid and karenitecin for melanoma. https://ClinicalTrials.gov/show/NCT00358319.
   Google Scholar
• A study of CPI-0209 in patients with advanced solid tumors and lymphomas. https://ClinicalTrials.gov/show/NCT04104776.
   Google Scholar
• DS-3201b and irinotecan for patients with recurrent small cell lung cancer. https://ClinicalTrials.gov/show/NCT03879798.
   Google Scholar
• Testing of tazemetostat in combination with topotecan and pembrolizumab in patients with recurrent small cell lung cancer. https://ClinicalTrials.gov/show/NCT05353439.
   Google Scholar
• Study of oral vorinostat in combination with topotecan in patients with chemosensitive recurrent SCLC. https://ClinicalTrials.gov/show/NCT00697476.
   Google Scholar
• Adhikari S, Bhattacharya A, Adhikary S, et al. The paradigm of drug resistance in cancer: an epigenetic perspective. Biosci Rep. 2022;42(4):BSR20211812.
   PubMed Web of Science ®Google Scholar