Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

ACC 2024 Congress

Catch up on all the top stories and latest evidence in cardiology research with our ACC 2024 Congress hub page.
ADVANCED SEARCH
Log in
Top
Targeted Oncology
Published in: Targeted Oncology 1/2018

01-02-2018 | Review Article

Incorporating DNA Methyltransferase Inhibitors (DNMTis) in the Treatment of Genitourinary Malignancies: A Systematic Review

Authors: Michal Chovanec, Fadi Taza, Maitri Kalra, Noah Hahn, Kenneth P. Nephew, Michael J. Spinella, Costantine Albany

Published in: Targeted Oncology | Issue 1/2018

Login to get access

Abstract

Inhibition of DNA methyltransferases (DNMTs) has emerged as a novel treatment strategy in solid tumors. Aberrant hypermethylation in promoters of critical tumor suppressor genes is the basis for the idea that treatment with hypomethylating agents may lead to the restoration of a “normal” epigenome and produce clinically meaningful therapeutic outcomes. The aim of this review article is to summarize the current state of knowledge of DNMT inhibitors in the treatment of genitourinary malignancies. The efficacy of these agents in genitourinary malignancies was reported in a number of studies and suggests a role of induced DNA hypomethylation in overcoming resistance to conventional cytotoxic treatments. The clinical significance of these findings should be further investigated.
Literature
1.
2.
3.
Herman JG, Baylin SB. Gene silencing in cancer in association with promoter hypermethylation. N Engl J Med. 2003;349:2042–54.PubMedCrossRef
4.
Becker PB, Workman JL. Nucleosome remodeling and epigenetics. Cold Spring Harb Perspect Biol. 2013;5
5.
Grunstein M. Histone acetylation in chromatin structure and transcription. Nature. 1997;389:349–52.PubMedCrossRef
6.
7.
8.
9.
10.
Jeschke J, Collignon E, Fuks F. DNA methylome profiling beyond promoters - taking an epigenetic snapshot of the breast tumor microenvironment. FEBS J. 2015;282:1801–14.PubMedCrossRef
11.
Yan W, Herman JG, Guo M. Epigenome-based personalized medicine in human cancer. Epigenomics. 2016;8:119–33.PubMedCrossRef
12.
Lister R, Pelizzola M, Dowen RH, Hawkins RD, Hon G, Tonti-Filippini J, et al. Human DNA methylomes at base resolution show widespread epigenomic differences. Nature. 2009;462:315–22.PubMedPubMedCentralCrossRef
13.
14.
Han H, Cortez CC, Yang X, Nichols PW, Jones PA, Liang G. DNA methylation directly silences genes with non-CpG island promoters and establishes a nucleosome occupied promoter. Hum Mol Genet. 2011;20:4299–310.PubMedPubMedCentralCrossRef
15.
Ziller MJ, Muller F, Liao J, Zhang Y, Gu H, Bock C, et al. Genomic distribution and inter-sample variation of non-CpG methylation across human cell types. PLoS Genet. 2011;7:e1002389.PubMedPubMedCentralCrossRef
16.
Kim H, Park J, Jung Y, Song SH, Han SW, Oh DY, et al. DNA methyltransferase 3-like affects promoter methylation of thymine DNA glycosylase independently of DNMT1 and DNMT3B in cancer cells. Int J Oncol. 2010;36:1563–72.PubMed
17.
Weisenberger DJ, Velicescu M, Cheng JC, Gonzales FA, Liang G, Jones PA. Role of the DNA methyltransferase variant DNMT3b3 in DNA methylation. Mol Cancer Res. 2004;2:62–72.PubMed
18.
Juttermann R, Li E, Jaenisch R. Toxicity of 5-aza-2′-deoxycytidine to mammalian cells is mediated primarily by covalent trapping of DNA methyltransferase rather than DNA demethylation. PNAS. 1994;91:11797–801.PubMedPubMedCentralCrossRef
19.
Orta ML, Pastor N, Burgos-Moron E, Dominguez I, Calderon-Montano JM, Huertas Castano C, et al. Zebularine induces replication-dependent double-strand breaks which are preferentially repaired by homologous recombination. DNA Repair (Amst). 2017;57:116–24.CrossRef
20.
Yoo CB, Jeong S, Egger G, Liang G, Phiasivongsa P, Tang C, et al. Delivery of 5-aza-2′-deoxycytidine to cells using oligodeoxynucleotides. Cancer Res. 2007;67:6400–8.PubMedCrossRef
21.
Yoo CB, Jeong S, Egger G, Liang G, Phiasivongsa P, Tang C, et al. Delivery of 5-Aza-2′-deoxycytidine to cells using oligodeoxynucleotides. Cancer Res. 2007;67:6400–8.PubMedCrossRef
22.
Cho M, Grabmaier K, Kitahori Y, Hiasa Y, Nakagawa Y, Uemura H, et al. Activation of the MN/CA9 gene is associated with hypomethylation in human renal cell carcinoma cell lines. Mol Carcinog. 2000;27:184–9.PubMedCrossRef
23.
Nguyen CT, Weisenberger DJ, Velicescu M, Gonzales FA, Lin JC, Liang G, et al. Histone H3-lysine 9 methylation is associated with aberrant gene silencing in cancer cells and is rapidly reversed by 5-aza-2′-deoxycytidine. Cancer Res. 2002;62:6456–61.PubMed
24.
Biswal BK, Beyrouthy MJ, Hever-Jardine MP, Armstrong D, Tomlinson CR, Christensen BC, et al. Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7:e53003.PubMedPubMedCentralCrossRef
25.
Sonnenburg D, Spinella MJ, Albany C. Epigenetic targeting of platinum resistant testicular cancer. Curr Cancer Drug Targets. 2016;16(9):789–95.
26.
Andersen JB, Factor VM, Marquardt JU, Raggi C, Lee YH, Seo D, et al. An integrated genomic and epigenomic approach predicts therapeutic response to zebularine in human liver cancer. Sci Transl Med. 2010;2:54ra77.PubMedPubMedCentral
27.
Zhao LX, Yun M, Kim HO, Lee JA, Choi WJ, Lee KM, et al. Design, synthesis, and anticancer activity of fluorocyclopentenyl-pyrimidines. Nucleic Acids Symp Ser (Oxf). 2005;(49):107–8.
28.
Jeong LS, Zhao LX, Choi WJ, Pal S, Park YH, Lee SK, et al. Synthesis and antitumor activity of fluorocyclopentenyl-pyrimidines. Nucleosides Nucleotides Nucleic Acids. 2007;26:713–6.PubMedCrossRef
29.
Choi WJ, Chung HJ, Chandra G, Alexander V, Zhao LX, Lee HW, et al. Fluorocyclopentenyl-cytosine with broad spectrum and potent antitumor activity. J Med Chem. 2012;55:4521–5.PubMedCrossRef
30.
Peters GJ, Smid K, Vecchi L, Kathmann I, Sarkisjan D, Honeywell RJ, et al. Metabolism, mechanism of action and sensitivity profile of fluorocyclopentenylcytosine (RX-3117; TV-1360). Investig New Drugs. 2013;31:1444–57.CrossRef
31.
Fournel M, Sapieha P, Beaulieu N, Besterman JM, MacLeod AR. Down-regulation of human DNA-(cytosine-5) methyltransferase induces cell cycle regulators p16(ink4A) and p21(WAF/Cip1) by distinct mechanisms. J Biol Chem. 1999;274:24250–6.PubMedCrossRef
32.
Arimany-Nardi C, Errasti-Murugarren E, Minuesa G, Martinez-Picado J, Gorboulev V, Koepsell H, et al. Nucleoside transporters and human organic cation transporter 1 determine the cellular handling of DNA-methyltransferase inhibitors. Br J Pharmacol. 2014;171:3868–80.PubMedPubMedCentralCrossRef
33.
Villar-Garea A, Fraga MF, Espada J, Esteller M. Procaine is a DNA-demethylating agent with growth-inhibitory effects in human cancer cells. Cancer Res. 2003;63:4984–9.PubMed
34.
Chuang JC, Yoo CB, Kwan JM, Li TW, Liang G, Yang AS, et al. Comparison of biological effects of non-nucleoside DNA methylation inhibitors versus 5-aza-2′-deoxycytidine. Mol Cancer Ther. 2005;4:1515–20.PubMedCrossRef
35.
Fang MZ, Wang Y, Ai N, Hou Z, Sun Y, Lu H, et al. Tea polyphenol (-)-epigallocatechin-3-gallate inhibits DNA methyltransferase and reactivates methylation-silenced genes in cancer cell lines. Cancer Res. 2003;63:7563–70.PubMed
36.
Brueckner B, Garcia Boy R, Siedlecki P, Musch T, Kliem HC, Zielenkiewicz P, et al. Epigenetic reactivation of tumor suppressor genes by a novel small-molecule inhibitor of human DNA methyltransferases. Cancer Res. 2005;65:6305–11.PubMedCrossRef
37.
Qin T, Si J, Raynal NJ, Wang X, Gharibyan V, Ahmed S, et al. Epigenetic synergy between decitabine and platinum derivatives. Clin Epigenetics. 2015;7:97.PubMedPubMedCentralCrossRef
38.
Van Tongelen A, Loriot A, De Smet C. Oncogenic roles of DNA hypomethylation through the activation of cancer-germline genes. Cancer Lett. 2017;396:130–7.PubMedCrossRef
39.
Matei D, Fang F, Shen C, Schilder J, Arnold A, Zeng Y, et al. Epigenetic resensitization to platinum in ovarian cancer. Cancer Res. 2012;72:2197–205.PubMedPubMedCentralCrossRef
40.
Tsai HC, Li H, Van Neste L, Cai Y, Robert C, Rassool FV, et al. Transient low doses of DNA-demethylating agents exert durable antitumor effects on hematological and epithelial tumor cells. Cancer Cell. 2012;21:430–46.PubMedPubMedCentralCrossRef
41.
Albany C, Hever-Jardine MP, von Herrmann KM, Yim CY, Tam J, Warzecha JM, et al. Refractory testicular germ cell tumors are highly sensitive to the second generation DNA methylation inhibitor guadecitabine. Oncotarget. 2017;8:2949–59.PubMedCrossRef
42.
Bouwman P, Jonkers J. The effects of deregulated DNA damage signalling on cancer chemotherapy response and resistance. Nat Rev Cancer. 2012;12:587–98.PubMedCrossRef
43.
Fang F, Munck J, Tang J, Taverna P, Wang Y, Miller DF, et al. The novel, small-molecule DNA methylation inhibitor SGI-110 as an ovarian cancer chemosensitizer. Clin Cancer Res. 2014;20:6504–16.PubMedPubMedCentralCrossRef
44.
Karpf AR, Lasek AW, Ririe TO, Hanks AN, Grossman D, Jones DA. Limited gene activation in tumor and normal epithelial cells treated with the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine. Mol Pharmacol. 2004;65:18–27.PubMedCrossRef
45.
Karpf AR, Peterson PW, Rawlins JT, Dalley BK, Yang Q, Albertsen H, et al. Inhibition of DNA methyltransferase stimulates the expression of signal transducer and activator of transcription 1, 2, and 3 genes in colon tumor cells. PNAS. 1999;96:14007–12.PubMedPubMedCentralCrossRef
46.
Gotwals P, Cameron S, Cipolletta D, Cremasco V, Crystal A, Hewes B, et al. Prospects for combining targeted and conventional cancer therapy with immunotherapy. Nat Rev Cancer. 2017;17:286–301.PubMedCrossRef
47.
Li H, Chiappinelli KB, Guzzetta AA, Easwaran H, Yen RW, Vatapalli R, et al. Immune regulation by low doses of the DNA methyltransferase inhibitor 5-azacitidine in common human epithelial cancers. Oncotarget. 2014;5:587–98.PubMedPubMedCentral
48.
Wang L, Amoozgar Z, Huang J, Saleh MH, Xing D, Orsulic S, et al. Decitabine enhances lymphocyte migration and function and synergizes with CTLA-4 blockade in a murine ovarian cancer model. Cancer Immunol Res. 2015;3:1030–41.PubMedCrossRef
49.
Dewannieux M, Heidmann T. Endogenous retroviruses: acquisition, amplification and taming of genome invaders. Curr Opin Virol. 2013;3:646–56.PubMedCrossRef
50.
Kassiotis G, Stoye JP. Immune responses to endogenous retroelements: taking the bad with the good. Nat Rev Immunol. 2016;16:207–19.PubMedCrossRef
51.
Chiappinelli KB, Strissel PL, Desrichard A, Li H, Henke C, Akman B, et al. Inhibiting DNA methylation causes an interferon response in cancer via dsRNA including endogenous retroviruses. Cell. 2015;162:974–86.PubMedPubMedCentralCrossRef
52.
Roulois D, Loo Yau H, Singhania R, Wang Y, Danesh A, Shen SY, et al. DNA-Demethylating agents target colorectal cancer cells by inducing viral mimicry by endogenous transcripts. Cell. 2015;162:961–73.PubMedPubMedCentralCrossRef
53.
Thompson PJ, Macfarlan TS, Lorincz MC. Long terminal repeats: from parasitic elements to building blocks of the transcriptional regulatory repertoire. Mol Cell. 2016;62:766–76.PubMedPubMedCentralCrossRef
54.
55.
Lind GE, Skotheim RI, Lothe RA. The epigenome of testicular germ cell tumors. APMIS. 2007;115:1147–60.PubMedCrossRef
56.
Netto GJ, Nakai Y, Nakayama M, Jadallah S, Toubaji A, Nonomura N, et al. Global DNA hypomethylation in intratubular germ cell neoplasia and seminoma, but not in nonseminomatous male germ cell tumors. Mod Pathol. 2008;21:1337–44.PubMedPubMedCentralCrossRef
57.
Wermann H, Stoop H, Gillis AJ, Honecker F, van Gurp RJ, Ammerpohl O, et al. Global DNA methylation in fetal human germ cells and germ cell tumours: association with differentiation and cisplatin resistance. J Pathol. 2010;221:433–42.PubMed
58.
Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA, et al. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2012;2:401–4.PubMedCrossRef
59.
Gao J, Aksoy BA, Dogrusoz U, Dresdner G, Gross B, Sumer SO, et al. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal. 2013;6:pl1.PubMedPubMedCentralCrossRef
60.
Koul S, Houldsworth J, Mansukhani MM, Donadio A, McKiernan JM, Reuter VE, et al. Characteristic promoter hypermethylation signatures in male germ cell tumors. Mol Cancer. 2002;1:8.PubMedPubMedCentralCrossRef
61.
Koul S, McKiernan JM, Narayan G, Houldsworth J, Bacik J, Dobrzynski DL, et al. Role of promoter hypermethylation in Cisplatin treatment response of male germ cell tumors. Mol Cancer. 2004;3:16.PubMedPubMedCentralCrossRef
62.
Beyrouthy MJ, Garner KM, Hever MP, Freemantle SJ, Eastman A, Dmitrovsky E, et al. High DNA methyltransferase 3B expression mediates 5-aza-deoxycytidine hypersensitivity in testicular germ cell tumors. Cancer Res. 2009;69:9360–6.PubMedPubMedCentralCrossRef
63.
Candelaria M, Gallardo-Rincon D, Arce C, Cetina L, Aguilar-Ponce JL, Arrieta O, 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;18:1529–38.PubMedCrossRef
64.
65.
Veerla S, Panagopoulos I, Jin Y, Lindgren D, Hoglund M. Promoter analysis of epigenetically controlled genes in bladder cancer. Genes Chromosomes Cancer. 2008;47:368–78.PubMedCrossRef
66.
Maruyama R, Toyooka S, Toyooka KO, Harada K, Virmani AK, Zochbauer-Muller S, et al. Aberrant promoter methylation profile of bladder cancer and its relationship to clinicopathological features. Cancer Res. 2001;61:8659–63.PubMed
67.
Bilgrami SM, Qureshi SA, Pervez S, Abbas F. Promoter hypermethylation of tumor suppressor genes correlates with tumor grade and invasiveness in patients with urothelial bladder cancer. Spring. 2014;3:178.CrossRef
68.
Wang X, Chen E, Yang X, Wang Y, Quan Z, Wu X, et al. 5-azacytidine inhibits the proliferation of bladder cancer cells via reversal of the aberrant hypermethylation of the hepaCAM gene. Oncol Rep. 2016;35:1375–84.
69.
Christoph F, Kempkensteffen C, Weikert S, Kollermann J, Krause H, Miller K, et al. Methylation of tumour suppressor genes APAF-1 and DAPK-1 and in vitro effects of demethylating agents in bladder and kidney cancer. Br J Cancer. 2006;95:1701–7.PubMedPubMedCentralCrossRef
70.
Hahn NM, Bonney PL, Dhawan D, Jones DR, Balch C, Guo Z, et al. Subcutaneous 5-azacitidine treatment of naturally occurring canine urothelial carcinoma: a novel epigenetic approach to human urothelial carcinoma drug development. J Urol. 2012;187:302–9.PubMed
71.
72.
Chuang JC, Warner SL, Vollmer D, Vankayalapati H, Redkar S, Bearss DJ, et al. S110, a 5-Aza-2′-deoxycytidine-containing dinucleotide, is an effective DNA methylation inhibitor in vivo and can reduce tumor growth. Mol Cancer Ther. 2010;9:1443–50.PubMedPubMedCentralCrossRef
73.
Cheng JC, Weisenberger DJ, Gonzales FA, Liang G, Xu GL, Hu YG, et al. Continuous zebularine treatment effectively sustains demethylation in human bladder cancer cells. Mol Cell Biol. 2004;24:1270–8.PubMedPubMedCentralCrossRef
74.
Cheng JC, Matsen CB, Gonzales FA, Ye W, Greer S, Marquez VE, et al. Inhibition of DNA methylation and reactivation of silenced genes by zebularine. J Natl Cancer Inst. 2003;95:399–409.PubMedCrossRef
75.
Ben-Kasus T, Ben-Zvi Z, Marquez VE, Kelley JA, Agbaria R. Metabolic activation of zebularine, a novel DNA methylation inhibitor, in human bladder carcinoma cells. Biochem Pharmacol. 2005;70:121–33.PubMedCrossRef
76.
Dote H, Cerna D, Burgan WE, Carter DJ, Cerra MA, Hollingshead MG, et al. Enhancement of in vitro and in vivo tumor cell radiosensitivity by the DNA methylation inhibitor zebularine. Clin Cancer Res. 2005;11:4571–9.PubMedCrossRef
77.
Qi D, Li J, Que B, Su J, Li M, Zhang C, et al. Long non-coding RNA DBCCR1-003 regulate the expression of DBCCR1 via DNMT1 in bladder cancer. Cancer Cell Int. 2016;16:81.PubMedPubMedCentralCrossRef
78.
Habuchi T, Luscombe M, Elder PA, Knowles MA. Structure and methylation-based silencing of a gene (DBCCR1) within a candidate bladder cancer tumor suppressor region at 9q32-q33. Genomics. 1998;48:277–88.PubMedCrossRef
79.
Chuang JC, Warner SL, Vollmer D, Vankayalapati H, Redkar S, Bearss DJ, et al. S110, a 5-Aza-2′-Deoxycytidine–containing dinucleotide, is an effective DNA Methylation inhibitor in vivo and can reduce tumor growth. Mol Cancer Ther. 2010;9:1443–50.PubMedPubMedCentralCrossRef
80.
Lin J, Gilbert J, Rudek MA, Zwiebel JA, Gore S, Jiemjit A, et al. A phase I dose-finding study of 5-azacytidine in combination with sodium phenylbutyrate in patients with refractory solid tumors. Clin Cancer Res. 2009;15:6241–9.PubMedPubMedCentralCrossRef
81.
Braiteh F, Soriano AO, Garcia-Manero G, Hong D, Johnson MM, Silva Lde P, et al. Phase I study of epigenetic modulation with 5-azacytidine and valproic acid in patients with advanced cancers. Clin Cancer Res. 2008;14:6296–301.PubMedPubMedCentralCrossRef
82.
Plummer R, Vidal L, Griffin M, Lesley M, de Bono J, Coulthard S, et al. Phase I study of MG98, an oligonucleotide antisense inhibitor of human DNA methyltransferase 1, given as a 7-day infusion in patients with advanced solid tumors. Clin Cancer Res. 2009;15:3177–83.PubMedCrossRef
83.
Kawakami T, Okamoto K, Ogawa O, Okada Y. Multipoint methylation and expression analysis of tumor suppressor genes in human renal cancer cells. Urology. 2003;61:226–30.PubMedCrossRef
84.
Avissar-Whiting M, Koestler DC, Houseman EA, Christensen BC, Kelsey KT, Marsit CJ. Polycomb group genes are targets of aberrant DNA methylation in renal cell carcinoma. Epigenetics. 2011;6:703–9.PubMedPubMedCentralCrossRef
85.
86.
Malouf GG, Su X, Zhang J, Creighton CJ, Ho TH, Lu Y, et al. DNA methylation signature reveals cell ontogeny of renal cell carcinomas. Clin Cancer Res. 2016;22:6236–46.PubMedPubMedCentralCrossRef
87.
Morris MR, Ricketts CJ, Gentle D, McRonald F, Carli N, Khalili H, et al. Genome-wide methylation analysis identifies epigenetically inactivated candidate tumour suppressor genes in renal cell carcinoma. Oncogene. 2011;30:1390–401.PubMedCrossRef
88.
Li M, Wang Y, Song Y, Bu R, Yin B, Fei X, et al. Aberrant DNA methyltransferase 1 expression in clear cell renal cell carcinoma development and progression. Chin J Cancer Res. 2014;26:371–81.PubMedPubMedCentral
89.
Peters I, Reese C, Dubrowinskaja N, Antonopoulos WI, Krause M, Dang TN, et al. DNA methylation signature for the assessment of metastatic risk in primary renal cell cancer. J Clin Oncol. 2017;35:516.CrossRef
90.
Ricketts CJ, Morris MR, Gentle D, Shuib S, Brown M, Clarke N, et al. Methylation profiling and evaluation of demethylating therapy in renal cell carcinoma. Clin Epigenetics. 2013;5:16.PubMedPubMedCentralCrossRef
91.
Alkamal I, Ikromov O, Tolle A, Fuller TF, Magheli A, Miller K, et al. An epigenetic screen unmasks metallothioneins as putative contributors to renal cell carcinogenesis. Urol Int. 2015;94:99–110.PubMedCrossRef
92.
Alleman WG, Tabios RL, Chandramouli GV, Aprelikova ON, Torres-Cabala C, Mendoza A, et al. The in vitro and in vivo effects of re-expressing methylated von Hippel-Lindau tumor suppressor gene in clear cell renal carcinoma with 5-aza-2′-deoxycytidine. Clin Cancer Res. 2004;10:7011–21.PubMedCrossRef
93.
Coral S, Parisi G, Nicolay HJ, Colizzi F, Danielli R, Fratta E, et al. Immunomodulatory activity of SGI-110, a 5-aza-2′-deoxycytidine-containing demethylating dinucleotide. Cancer Immunol Immunother. 2013;62:605–14.PubMedCrossRef
94.
Reu FJ, Bae SI, Cherkassky L, Leaman DW, Lindner D, Beaulieu N, et al. Overcoming resistance to interferon-induced apoptosis of renal carcinoma and melanoma cells by DNA demethylation. J Clin Oncol. 2006;24:3771–9.PubMedCrossRef
95.
Chiam K, Centenera MM, Butler LM, Tilley WD, Bianco-Miotto T. GSTP1 DNA methylation and expression status is indicative of 5-aza-2′-deoxycytidine efficacy in human prostate cancer cells. PLoS One. 2011;6:e25634.PubMedPubMedCentralCrossRef
96.
Ikromov O, Alkamal I, Magheli A, Ratert N, Sendeski M, Miller K, et al. Functional epigenetic analysis of prostate carcinoma: a role for seryl-tRNA synthetase? J Biomark. 2014;2014:362164.PubMedPubMedCentralCrossRef
97.
Sabatino MA, Geroni C, Ganzinelli M, Ceruti R, Broggini M. Zebularine partially reverses GST methylation in prostate cancer cells and restores sensitivity to the DNA minor groove binder brostallicin. Epigenetics. 2013;8:656–65.PubMedPubMedCentralCrossRef
98.
Collard RL, Harya NS, Monzon FA, Maier CE, O’Keefe DS. Methylation of the ASC gene promoter is associated with aggressive prostate cancer. Prostate. 2006;66:687–95.PubMedCrossRef
99.
Gertych A, Oh JH, Wawrowsky KA, Weisenberger DJ, Tajbakhsh J. 3-D DNA methylation phenotypes correlate with cytotoxicity levels in prostate and liver cancer cell models. BMC Pharmacol Toxicol. 2013;14:11.PubMedPubMedCentralCrossRef
100.
Kim TD, Jin F, Shin S, Oh S, Lightfoot SA, Grande JP, et al. Histone demethylase JMJD2A drives prostate tumorigenesis through transcription factor ETV1. J Clin Invest. 2016;126:706–20.PubMedPubMedCentralCrossRef
101.
Festuccia C, Gravina GL, D'Alessandro AM, Muzi P, Millimaggi D, Dolo V, et al. Azacitidine improves antitumor effects of docetaxel and cisplatin in aggressive prostate cancer models. Endocr Relat Cancer. 2009;16:401–13.PubMedCrossRef
102.
Frost P, Abbruzzese JL, Hunt B, Lee D, Ellis M. Synergistic cytotoxicity using 2′-deoxy-5-azacytidine and cisplatin or 4-hydroperoxycyclophosphamide with human tumor cells. Cancer Res. 1990;50:4572–7.PubMed
103.
Kagey JD, Kapoor-Vazirani P, McCabe MT, Powell DR, Vertino PM. Long-term stability of demethylation after transient exposure to 5-aza-2′-deoxycytidine correlates with sustained RNA polymerase II occupancy. Mol Cancer Res. 2010;8:1048–59.PubMedPubMedCentralCrossRef
104.
McCabe MT, Low JA, Daignault S, Imperiale MJ, Wojno KJ, Day ML. Inhibition of DNA methyltransferase activity prevents tumorigenesis in a mouse model of prostate cancer. Cancer Res. 2006;66:385–92.PubMedCrossRef
105.
Sonpavde G, Aparicio AM, Zhan F, North B, Delaune R, Garbo LE, et al. Azacitidine favorably modulates PSA kinetics correlating with plasma DNA LINE-1 hypomethylation in men with chemonaive castration-resistant prostate cancer. Urol Oncol. 2011;29:682–9.PubMedCrossRef
106.
Singal R, Ramachandran K, Gordian E, Quintero C, Zhao W, Reis IM. Phase I/II study of azacitidine, docetaxel, and prednisone in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel-based therapy. Clin Genitourin Cancer. 2015;13:22–31.PubMedCrossRef
107.
Rudek MA, Zhao M, He P, Hartke C, Gilbert J, Gore SD, et al. Pharmacokinetics of 5-azacitidine administered with phenylbutyrate in patients with refractory solid tumors or hematologic malignancies. J Clin Oncol. 2005;23:3906–11.PubMedCrossRef
108.
Wong CM, Wong CC, Ng YL, Au SL, Ko FC, Ng IO. Transcriptional repressive H3K9 and H3K27 methylations contribute to DNMT1-mediated DNA methylation recovery. PLoS One. 2011;6:e16702.PubMedPubMedCentralCrossRef
109.
110.
Feber A, Arya M, de Winter P, Saqib M, Nigam R, Malone PR, et al. Epigenetics markers of metastasis and HPV-induced tumorigenesis in penile cancer. Clin Cancer Res. 2015;21:1196–206.PubMedCrossRef
111.
Kuasne H, Colus IM, Busso AF, Hernandez-Vargas H, Barros-Filho MC, Marchi FA, et al. Genome-wide methylation and transcriptome analysis in penile carcinoma: uncovering new molecular markers. Clin Epigenetics. 2015;7:46.PubMedPubMedCentralCrossRef
Metadata
Title
Incorporating DNA Methyltransferase Inhibitors (DNMTis) in the Treatment of Genitourinary Malignancies: A Systematic Review
Authors
Michal Chovanec
Fadi Taza
Maitri Kalra
Noah Hahn
Kenneth P. Nephew
Michael J. Spinella
Costantine Albany
Publication date
01-02-2018
Publisher
Springer International Publishing
Published in
Targeted Oncology / Issue 1/2018
Print ISSN: 1776-2596
Electronic ISSN: 1776-260X
DOI
https://doi.org/10.1007/s11523-017-0546-x

Other articles of this Issue 1/2018

Targeted Oncology 1/2018 Go to the issue

Current Opinion

Motivation for Launching a Cancer Metastasis Inhibition (CMI) Program

Leading Article

Immune Checkpoint Blockade: The New Frontier in Cancer Treatment

Original Research Article

A phase II Study Evaluating Combined Neoadjuvant Cetuximab and Chemotherapy Followed by Chemoradiotherapy and Concomitant Cetuximab in Locoregional Oesophageal Cancer Patients

Review Article

The Role of B-Cell Maturation Antigen in the Biology and Management of, and as a Potential Therapeutic Target in, Multiple Myeloma

Original Research Article

Phase IB Trial of the Anti-Cancer Stem Cell DLL4-Binding Agent Demcizumab with Pemetrexed and Carboplatin as First-Line Treatment of Metastatic Non-Squamous NSCLC

Short Communication

Trastuzumab in Combination with FOLFIRI in Patients with Advanced HER2-Positive Gastro-Esophageal Adenocarcinoma: A Retrospective Multicenter AGEO Study
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits