Cancer Treatment: An Epigenetic View

Abstract

Cancer can be identified as an uncontrolled growth and reproduction of cell. Accumulation of genetic aberrations (mutations of oncogenes and tumor-suppressor genes and epigenetic modifications) is one of the characteristics of cancer cell. Increasing number of studies highlighted importance of the epigenetic alterations in cancer treatment and prognosis. Now, cancer epigenetics have a huge importance for developing novel biomarkers and therapeutic target for cancer. In this review, we will provide a summary of the major epigenetic changes involved in cancer and preclinical results of epigenetic therapeutics.

Keywords

cancer / treatment / epigenetics / epidrugs / methylation

Conflict of Interest

None declared.

References

[1] Mai A, Altucci L. Epi-drugs to fight cancer: from chemistry to cancer treatment, the road ahead. Int J Biochem Cell Biol 2009; 41(01): 199-213

[2] Esteller M. Epigenetics in cancer. N Engl J Med 2008; 358(11): 1148-1159

[3] Svedružić ŽM. Dnmt1 structure and function. Prog Mol Biol Transl Sci 2011; 101: 221-254

[4] Yu J, Xie T, Wang Z, et al. DNA methyltransferases: emerging targets for the discovery of inhibitors as potent anticancer drugs. Drug Discov Today 2019; 24(12): 2323-2331

[5] Fukushige S, Horii A. DNA methylation in cancer: a gene silencing mechanism and the clinical potential of its biomarkers. Tohoku J Exp Med 2013; 229(03): 173-185

[6] Sandoval J, Esteller M. Cancer epigenomics: beyond genomics. Curr Opin Genet Dev 2012; 22(01): 50-55

[7] Audia JE, Campbell RM. Histone modifications and cancer. Cold Spring Harb Perspect Biol 2016; 8(04): a019521

[8] Kim JE. Bookmarking by histone methylation ensures chromosomal integrity during mitosis. Arch Pharm Res 2019; 42(06): 466-480

[9] Erdel F. How communication between nucleosomes enables spreading and epigenetic memory of histone modifications. BioEssays2017 39. (12)

[10] Kutateladze TG, Gozani O, Bienz M, Ostankovitch M. Histone modifications for chromatin dynamics and cellular plasticity. J Mol Biol 2017; 429(13): 1921-1923

[11] Esteller M. Epigenetic drugs: more than meets the eye. Epigenetics 2017; 12(05): 307

[12] Esteller M. Cancer epigenomics: DNA methylomes and histone-modification maps. Nat Rev Genet 2007; 8(04): 286-298

[13] Xin B, Rohs R. Relationship between histone modifications and transcription factor binding is protein family specific. Genome Res 2018

[14] Kulis M, Esteller M. DNA methylation and cancer. Adv Genet 2010; 70: 27-56

[15] Ehrlich M. DNA hypomethylation in cancer cells. Epigenomics 2009; 1(02): 239-259

[16] Tse JWT, Jenkins LJ, Chionh F, Mariadason JM. Aberrant DNA Methylation in Colorectal Cancer: What Should We Target?. Trends Cancer 2017; 3(10): 698-712

[17] Deng P, Chang XJ, Gao ZM, et al. Downregulation and DNA methylation of ECRG4 in gastric cancer. OncoTargets Ther 2018; 11: 4019-4028

[18] Liloglou T, Bediaga NG, Brown BR, Field JK, Davies MP. Epigenetic biomarkers in lung cancer. Cancer Lett 2014; 342(02): 200-212

[19] Anwar SL, Lehmann U. DNA methylation, microRNAs, and their crosstalk as potential biomarkers in hepatocellular carcinoma. World J Gastroenterol 2014; 20(24): 7894-7913

[20] Faryna M, Konermann C, Aulmann S, et al. Genome-wide methylation screen in low-grade breast cancer identifies novel epigenetically altered genes as potential biomarkers for tumor diagnosis. FASEB J 2012; 26(12): 4937-4950

[21] Lund RJ, Huhtinen K, Salmi J, et al. DNA methylation and transcriptome changes associated with cisplatin resistance in ovarian cancer. Sci Rep 2017; 7(01): 1469

[22] Putiri EL, Robertson KD. Epigenetic mechanisms and genome stability. Clin Epigenetics 2011; 2(02): 299-314

[23] Toyota M, Suzuki H, Yamashita T, et al. Cancer epigenomics: implications of DNA methylation in personalized cancer therapy. Cancer Sci 2009; 100(05): 787-791

[24] Soshnev AA, Josefowicz SZ, Allis CD. Greater than the sum of parts: complexity of the dynamic epigenome. Mol Cell 2016; 62(05): 681-694

[25] Irizarry RA, Ladd-Acosta C, Wen B, et al. The human colon cancer methylome shows similar hypo- and hypermethylation at conserved tissue-specific CpG island shores. Nat Genet 2009; 41(02): 178-186

[26] Peedicayil J. The role of DNA methylation in the pathogenesis and treatment of cancer. Curr Clin Pharmacol 2012; 7(04): 333-340

[27] Castillo-Aguilera O, Depreux P, Halby L, Arimondo PB, Goossens L. DNA methylation targeting: the DNMT/HMT crosstalk challenge. Biomolecules 2017; 7(01): E3

[28] Miller CM, Harris EN. Antisense oligonucleotides: treatment strategies and cellular internalization. RNA Dis 2016; 3(04): e1393

[29] Xu P, Hu G, Luo C, Liang Z. DNA methyltransferase inhibitors: an updated patent review (2012-2015). Expert Opin Ther Pat 2016; 26(09): 1017-1030

[30] Heuser M, Yun H, Thol F. Epigenetics in myelodysplastic syndromes. Semin Cancer Biol 2018; 51: 170-179

[31] Jiang LC, Luo JM. Role and mechanism of decitabine combined with tyrosine kinase inhibitors in advanced chronic myeloid leukemia cells. Oncol Lett 2017; 14(02): 1295-1302

[32] Orta ML, Pastor N, Burgos-Morón E, et al. Zebularine induces replication-dependent double-strand breaks which are preferentially repaired by homologous recombination. DNA Repair (Amst) 2017; 57: 116-124

[33] Schrump DS, Fischette MR, Nguyen DM, et al. Phase I study of decitabine-mediated gene expression in patients with cancers involving the lungs, esophagus, or pleura. Clin Cancer Res 2006; 12(19): 5777-5785

[34] Gros C, Fahy J, Halby L, et al. DNA methylation inhibitors in cancer: recent and future approaches. Biochimie 2012; 94(11): 2280-2296

[35] Subramaniam D, Thombre R, Dhar A, Anant S. DNA methyltransferases: a novel target for prevention and therapy. Front Oncol 2014; 4: 80

[36] Khan N, Afaq F, Saleem M, Ahmad N, Mukhtar H. Targeting multiple signaling pathways by green tea polyphenol (-)-epigallocatechin-3-gallate. Cancer Res 2006; 66(05): 2500-2505

[37] Fang MZ, Wang Y, Ai N, et al. Tea polyphenol (-)-epigallocatechin-3-gallate inhibits DNA methyltransferase and reactivates methylation-silenced genes in cancer cell lines. Cancer Res 2003; 63(22): 7563-7570

[38] 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(16): 4984-4989

[39] Parker BS, Cutts SM, Nudelman A, Rephaeli A, Phillips DR, Sukumar S. Mitoxantrone mediates demethylation and reexpression of cyclin d2, estrogen receptor and 14.3.3sigma in breast cancer cells. Cancer Biol Ther 2003; 2(03): 259-263

[40] Zhang C, Zhong JF, Stucky A, Chen X-L, Press MF, Zhang X.Histone acetylation: novel target for the treatment of acute lymphoblastic leukemia. Clin Epigenetics 2015; 7: 117

[41] Morris MJ, Monteggia LM. Unique functional roles for class I and class II histone deacetylases in central nervous system development and function. Int J Dev Neurosci 2013; 31(06): 370-381

[42] Mottamal M, Zheng S, Huang TL, Wang G. Histone deacetylase inhibitors in clinical studies as templates for new anticancer agents. Molecules 2015; 20(03): 3898-3941

[43] Barneda-Zahonero B, Parra M. Histone deacetylases and cancer. Mol Oncol 2012; 6(06): 579-589

[44] Byrd JC, Marcucci G, Parthun MR, et al. A phase 1 and pharmacodynamic study of depsipeptide (FK228) in chronic lymphocytic leukemia and acute myeloid leukemia. Blood 2005; 105(03): 959-967

[45] Pilatrino C, Cilloni D, Messa E, et al. Increase in platelet count in older, poor-risk patients with acute myeloid leukemia or myelodysplastic syndrome treated with valproic acid and all-trans retinoic acid. Cancer 2005; 104(01): 101-109

[46] Gilbert J, Baker SD, Bowling MK, et al. A phase I dose escalation and bioavailability study of oral sodium phenylbutyrate in patients with refractory solid tumor malignancies. Clin Cancer Res 2001; 7(08): 2292-2300

[47] Ryan QC, Headlee D, Acharya M, et al. Phase I and pharmacokinetic study of MS-275, a histone deacetylase inhibitor, in patients with advanced and refractory solid tumors or lymphoma. J Clin Oncol 2005; 23(17): 3912-3922

[48] Zeller C, Brown R. Therapeutic modulation of epigenetic drivers of drug resistance in ovarian cancer. Ther Adv Med Oncol 2010; 2(05): 319-329

[49] Steele N, Finn P, Brown R, Plumb JA. Combined inhibition of DNA methylation and histone acetylation enhances gene re-expression and drug sensitivity in vivo. Br J Cancer 2009; 100(05): 758-763

[50] Cameron EE, Bachman KE, Myöhänen S, Herman JG, Baylin SB. Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer. Nat Genet 1999; 21(01): 103-107

[51] Yang X, Phillips DL, Ferguson AT, Nelson WG, Herman JG, Davidson NE. Synergistic activation of functional estrogen receptor (ER)-alpha by DNA methyltransferase and histone deacetylase inhibition in human ER-alpha-negative breast cancer cells. Cancer Res 2001; 61(19): 7025-7029

[52] Gore SD, Baylin S, Sugar E, et al. Combined DNA methyltransferase and histone deacetylase inhibition in the treatment of myeloid neoplasms. Cancer Res 2006; 66(12): 6361-6369

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Global Medical Genetics