Review Article

Epigenetic Therapies and Potential Drugs for Treating Human Cancer

Author(s): Shi-qi Lin and Xia Li*

Volume 21, Issue 11, 2020

Page: [1068 - 1083] Pages: 16

DOI: 10.2174/1389450121666200325093104

Price: $65

Abstract

Epigenetic modifications ensure the maintenance of normal cellular functions, and their dysregulation is frequently found in many disease states, including cancer. Nowadays, the most studied epigenetic dysregulation associated with tumorigenesis, cancer progression and metastasis refers to the variations in DNA methylation, histone modification and chromatin structure. The development of novel agents targeting these processes has enabled us to open up new pathways for anti-cancer strategies. To date, many small molecules have been designed to target epigenetic modifiers, and some of them are currently in clinical trials for patients with haematologic malignancies and solid tumours. With this in mind, we elaborate on basic information on epigenetic modifications and potential epigenetic therapies for cancer treatment.

Keywords: Epigenetic, DNA methylation, Histones, epigenetic drugs, cancer, therapies.

Graphical Abstract
[1]
Waddington CH. Towards a theoretical biology. Nature 1968; 218(5141): 525-7.
[http://dx.doi.org/10.1038/218525a0] [PMID: 5650959]
[2]
Wu Ct, Morris JR. Genes, genetics, and epigenetics: a correspondence. Science 2001; 293(5532): 1103-5.
[http://dx.doi.org/10.1126/science.293.5532.1103] [PMID: 11498582]
[3]
Saxonov S, Berg P, Brutlag DL. A genome-wide analysis of CpG dinucleotides in the human genome distinguishes two distinct classes of promoters. Proc Natl Acad Sci USA 2006; 103(5): 1412-7.
[http://dx.doi.org/10.1073/pnas.0510310103] [PMID: 16432200]
[4]
Herman JG, Baylin SB. Gene silencing in cancer in association with promoter hypermethylation. N Engl J Med 2003; 349(21): 2042-54.
[http://dx.doi.org/10.1056/NEJMra023075] [PMID: 14627790]
[5]
Rodriguez C, Borgel J, Court F, Cathala G, Forné T, Piette J. CTCF is a DNA methylation-sensitive positive regulator of the INK/ARF locus. Biochem Biophys Res Commun 2010; 392(2): 129-34.
[http://dx.doi.org/10.1016/j.bbrc.2009.12.159] [PMID: 20051228]
[6]
Kornberg RD. Chromatin structure: a repeating unit of histones and DNA. Science 1974; 184(4139): 868-71.
[http://dx.doi.org/10.1126/science.184.4139.868] [PMID: 4825889]
[7]
Paul AL, Ferl RJ. Higher-order chromatin structure: looping long molecules. Plant Mol Biol 1999; 41(6): 713-20.
[http://dx.doi.org/10.1023/A:1006323222693] [PMID: 10737136]
[8]
Ren B, Chen ES. Regulation of centromeric heterochromatin in the cell cycle by phosphorylation of histone H3 tyrosine 41. Curr Genet 2019; 65(4): 829-36.
[http://dx.doi.org/10.1007/s00294-019-00962-2] [PMID: 30963244]
[9]
Hansen KD, Timp W, Bravo HC, et al. Increased methylation variation in epigenetic domains across cancer types. Nat Genet 2011; 43(8): 768-75.
[http://dx.doi.org/10.1038/ng.865] [PMID: 21706001]
[10]
Vandiver AR, Irizarry RA, Hansen KD, et al. Age and sun exposure-related widespread genomic blocks of hypomethylation in nonmalignant skin. Genome Biol 2015; 16: 80.
[http://dx.doi.org/10.1186/s13059-015-0644-y] [PMID: 25886480]
[11]
Heyn H, Vidal E, Ferreira HJ, et al. Epigenomic analysis detects aberrant super-enhancer DNA methylation in human cancer. Genome Biol 2016; 17: 11.
[http://dx.doi.org/10.1186/s13059-016-0879-2] [PMID: 26813288]
[12]
Feinberg AP, Vogelstein B. Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature 1983; 301(5895): 89-92.
[http://dx.doi.org/10.1038/301089a0] [PMID: 6185846]
[13]
Hanada M, Delia D, Aiello A, Stadtmauer E, Reed JC. bcl-2 gene hypomethylation and high-level expression in B-cell chronic lymphocytic leukemia. Blood 1993; 82(6): 1820-8.
[http://dx.doi.org/10.1182/blood.V82.6.1820.1820] [PMID: 8104532]
[14]
Smiraglia DJ, Rush LJ, Frühwald MC, et al. Excessive CpG island hypermethylation in cancer cell lines versus primary human malignancies. Hum Mol Genet 2001; 10(13): 1413-9.
[http://dx.doi.org/10.1093/hmg/10.13.1413] [PMID: 11440994]
[15]
Greger V, Passarge E, Höpping W, Messmer E, Horsthemke B. Epigenetic changes may contribute to the formation and spontaneous regression of retinoblastoma. Hum Genet 1989; 83(2): 155-8.
[http://dx.doi.org/10.1007/BF00286709] [PMID: 2550354]
[16]
Xing XB, Cai WB, Luo L, Liu LS, Shi HJ, Chen MH. The Prognostic Value of p16 Hypermethylation in Cancer: A Meta-Analysis. PLoS One 2013; 8(6)e66587
[http://dx.doi.org/10.1371/journal.pone.0066587] [PMID: 23805242]
[17]
Uysal F, Akkoyunlu G, Ozturk S. DNA methyltransferases exhibit dynamic expression during spermatogenesis. Reprod Biomed Online 2016; 33(6): 690-702.
[http://dx.doi.org/10.1016/j.rbmo.2016.08.022] [PMID: 27687053]
[18]
Walton EL, Francastel C, Velasco G. Maintenance of DNA methylation: Dnmt3b joins the dance. Epigenetics 2011; 6(11): 1373-7.
[http://dx.doi.org/10.4161/epi.6.11.17978] [PMID: 22048250]
[19]
Santi DV, Norment A, Garrett CE. Covalent bond formation between a DNA-cytosine methyltransferase and DNA containing 5-azacytosine. Proc Natl Acad Sci USA 1984; 81(22): 6993-7.
[http://dx.doi.org/10.1073/pnas.81.22.6993] [PMID: 6209710]
[20]
Ghoshal K, Datta J, Majumder S, et al. 5-Aza-deoxycytidine induces selective degradation of DNA methyltransferase 1 by a proteasomal pathway that requires the KEN box, bromo-adjacent homology domain, and nuclear localization signal. Mol Cell Biol 2005; 25(11): 4727-41.
[http://dx.doi.org/10.1128/MCB.25.11.4727-4741.2005] [PMID: 15899874]
[21]
Derissen EJB, Beijnen JH, Schellens JHM. Concise drug review: azacitidine and decitabine. Oncologist 2013; 18(5): 619-24.
[http://dx.doi.org/10.1634/theoncologist.2012-0465] [PMID: 23671007]
[22]
Zhou L, Cheng X, Connolly BA, Dickman MJ, Hurd PJ, Hornby DP. Zebularine: a novel DNA methylation inhibitor that forms a covalent complex with DNA methyltransferases. J Mol Biol 2002; 321(4): 591-9.
[http://dx.doi.org/10.1016/S0022-2836(02)00676-9] [PMID: 12206775]
[23]
Sarkisjan D, Pronk F, Kuin R, el Hassouni B, Lee YB, Kim DJ, et al. RX-3117 promotes epigenetic effects in cancer cells through enhanced degradation of DNMT1. Cancer Res 2018; 78(13)
[24]
Issa JJ, Roboz G, Rizzieri D, et al. Safety and tolerability of guadecitabine (SGI-110) in patients with myelodysplastic syndrome and acute myeloid leukaemia: a multicentre, randomised, dose-escalation phase 1 study. Lancet Oncol 2015; 16(9): 1099-110.
[http://dx.doi.org/10.1016/S1470-2045(15)00038-8] [PMID: 26296954]
[25]
Brueckner B, Rius M, Markelova MR, et al. Delivery of 5-azacytidine to human cancer cells by elaidic acid esterification increases therapeutic drug efficacy. Mol Cancer Ther 2010; 9(5): 1256-64.
[http://dx.doi.org/10.1158/1535-7163.MCT-09-1202] [PMID: 20442313]
[26]
Song SH, Han SW, Bang YJ. Epigenetic-based therapies in cancer: progress to date. Drugs 2011; 71(18): 2391-403.
[http://dx.doi.org/10.2165/11596690-000000000-00000] [PMID: 22141383]
[27]
Siedlecki P, Garcia Boy R, Musch T, et al. Discovery of two novel, small-molecule inhibitors of DNA methylation. J Med Chem 2006; 49(2): 678-83.
[http://dx.doi.org/10.1021/jm050844z] [PMID: 16420053]
[28]
Brueckner B, Garcia Boy R, Siedlecki P, et al. Epigenetic reactivation of tumor suppressor genes by a novel small-molecule inhibitor of human DNA methyltransferases. Cancer Res 2005; 65(14): 6305-11.
[http://dx.doi.org/10.1158/0008-5472.CAN-04-2957] [PMID: 16024632]
[29]
Suzuki T, Tanaka R, Hamada S, Nakagawa H, Miyata N. Design, synthesis, inhibitory activity, and binding mode study of novel DNA methyltransferase 1 inhibitors. Bioorg Med Chem Lett 2010; 20(3): 1124-7.
[http://dx.doi.org/10.1016/j.bmcl.2009.12.016] [PMID: 20056538]
[30]
Kuck D, Singh N, Lyko F, Medina-Franco JL. Novel and selective DNA methyltransferase inhibitors: Docking-based virtual screening and experimental evaluation. Bioorg Med Chem 2010; 18(2): 822-9.
[http://dx.doi.org/10.1016/j.bmc.2009.11.050] [PMID: 20006515]
[31]
Goffin J, Eisenhauer E. DNA methyltransferase inhibitors-state of the art. Ann Oncol 2002; 13(11): 1699-716.
[http://dx.doi.org/10.1093/annonc/mdf314] [PMID: 12419742]
[32]
Plummer R, Vidal L, Griffin M, 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(9): 3177-83.
[http://dx.doi.org/10.1158/1078-0432.CCR-08-2859] [PMID: 19383817]
[33]
Winquist E, Knox J, Ayoub JP, et al. Phase II trial of DNA methyltransferase 1 inhibition with the antisense oligonucleotide MG98 in patients with metastatic renal carcinoma: a National Cancer Institute of Canada Clinical Trials Group investigational new drug study. Invest New Drugs 2006; 24(2): 159-67.
[http://dx.doi.org/10.1007/s10637-006-5938-1] [PMID: 16502349]
[34]
Graça I, Sousa EJ, Costa-Pinheiro P, et al. Anti-neoplastic properties of hydralazine in prostate cancer. Oncotarget 2014; 5(15): 5950-64.
[http://dx.doi.org/10.18632/oncotarget.1909] [PMID: 24797896]
[35]
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): 4984-9.
[PMID: 12941824]
[36]
He Y-F, Li B-Z, Li Z, et al. Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA. Science 2011; 333(6047): 1303-7.
[http://dx.doi.org/10.1126/science.1210944] [PMID: 21817016]
[37]
Ito S, Shen L, Dai Q, et al. Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine. Science 2011; 333(6047): 1300-3.
[http://dx.doi.org/10.1126/science.1210597] [PMID: 21778364]
[38]
Cimmino L, Dolgalev I, Wang Y, et al. Restoration of TET2 Function Blocks Aberrant Self-Renewal and Leukemia Progression. Cell 2017; 170(6): 1079-1095.e20.
[http://dx.doi.org/10.1016/j.cell.2017.07.032] [PMID: 28823558]
[39]
Thienpont B, Steinbacher J, Zhao H, et al. Tumour hypoxia causes DNA hypermethylation by reducing TET activity. Nature 2016; 537(7618): 63-8.
[http://dx.doi.org/10.1038/nature19081] [PMID: 27533040]
[40]
Tefferi A, Lasho TL, Abdel-Wahab O, et al. IDH1 and IDH2 mutation studies in 1473 patients with chronic-, fibrotic- or blast-phase essential thrombocythemia, polycythemia vera or myelofibrosis. Leukemia 2010; 24(7): 1302-9.
[http://dx.doi.org/10.1038/leu.2010.113] [PMID: 20508616]
[41]
Visani M, Acquaviva G, Marucci G, et al. Non-canonical IDH1 and IDH2 mutations: a clonal and relevant event in an Italian cohort of gliomas classified according to the 2016 World Health Organization (WHO) criteria. J Neurooncol 2017; 135(2): 245-54.
[http://dx.doi.org/10.1007/s11060-017-2571-0] [PMID: 28748342]
[42]
Borger DR, Tanabe KK, Fan KC, et al. Frequent mutation of isocitrate dehydrogenase (IDH)1 and IDH2 in cholangiocarcinoma identified through broad-based tumor genotyping. Oncologist 2012; 17(1): 72-9.
[http://dx.doi.org/10.1634/theoncologist.2011-0386] [PMID: 22180306]
[43]
Arai M, Nobusawa S, Ikota H, Takemura S, Nakazato Y. Frequent IDH1/2 mutations in intracranial chondrosarcoma: a possible diagnostic clue for its differentiation from chordoma. Brain Tumor Pathol 2012; 29(4): 201-6.
[http://dx.doi.org/10.1007/s10014-012-0085-1] [PMID: 22323113]
[44]
Ward PS, Patel J, Wise DR, et al. The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate. Cancer Cell 2010; 17(3): 225-34.
[http://dx.doi.org/10.1016/j.ccr.2010.01.020] [PMID: 20171147]
[45]
Gao Y, Fan B, Le K, Manyak E, Yang H, Yen K, et al. Evaluation of the Pharmacokinetics of AG-221, a Potent Mutant IDH2 Inhibitor, in Patients with IDH2-Mutation Positive Advanced Hematologic Malignancies in a Phase 1/2 Trial. Blood 2015; 126(23)
[http://dx.doi.org/10.1182/blood.V126.23.2509.2509]
[46]
DiNardo CD, Foran JM, Watts JM, Stein EM, De Botton S, Fathi AT, et al. Ivosidenib (IVO; AG-120) in IDH1-Mutant Relapsed or Refractory Myelodysplastic Syndrome: Updated Results from a Phase 1 Study. Clinical Lymphoma Myeloma & leukemia 2019; 19: S340.
[47]
DiNardo CD, Roboz GJ, Stein EM, de Botton S, Mims AS, Prince GT, et al. Ivosidenib (IVO; AG-120) in IDH1-Mutant Newly- Diagnosed Acute Myeloid Leukemia (ND AML): Updated Results from a Phase 1 Study. Clinical Lymphoma Myeloma & Leukemia 2019; 19: S220.
[48]
Davis MI, Gross S, Shen M, et al. Biochemical, cellular, and biophysical characterization of a potent inhibitor of mutant isocitrate dehydrogenase IDH1. J Biol Chem 2014; 289(20): 13717-25.
[http://dx.doi.org/10.1074/jbc.M113.511030] [PMID: 24668804]
[49]
Gerecke C, Schumacher F, Berndzen A, Homann T, Kleuser B. Vitamin C in combination with inhibition of mutant IDH1 synergistically activates TET enzymes and epigenetically modulates gene silencing in colon cancer cells. Epigenetics 2019; 1-16.
[PMID: 31505989]
[50]
Park JW, Han J-W. Targeting epigenetics for cancer therapy. Arch Pharm Res 2019; 42(2): 159-70.
[http://dx.doi.org/10.1007/s12272-019-01126-z] [PMID: 30806885]
[51]
Marmorstein R, Roth SY. Histone acetyltransferases: function, structure, and catalysis. Curr Opin Genet Dev 2001; 11(2): 155-61.
[http://dx.doi.org/10.1016/S0959-437X(00)00173-8] [PMID: 11250138]
[52]
Spange S, Wagner T, Heinzel T, Krämer OH. Acetylation of non-histone proteins modulates cellular signalling at multiple levels. Int J Biochem Cell Biol 2009; 41(1): 185-98.
[http://dx.doi.org/10.1016/j.biocel.2008.08.027] [PMID: 18804549]
[53]
Iyer NG, Ozdag H, Caldas C. p300/CBP and cancer. Oncogene 2004; 23(24): 4225-31.
[http://dx.doi.org/10.1038/sj.onc.1207118] [PMID: 15156177]
[54]
Yang XJ. The diverse superfamily of lysine acetyltransferases and their roles in leukemia and other diseases. Nucleic Acids Res 2004; 32(3): 959-76.
[http://dx.doi.org/10.1093/nar/gkh252] [PMID: 14960713]
[55]
Gao XN, Lin J, Ning QY, et al. A histone acetyltransferase p300 inhibitor C646 induces cell cycle arrest and apoptosis selectively in AML1-ETO-positive AML cells. PLoS One 2013; 8(2)e55481
[http://dx.doi.org/10.1371/journal.pone.0055481] [PMID: 23390536]
[56]
Stimson L, Rowlands MG, Newbatt YM, et al. Isothiazolones as inhibitors of PCAF and p300 histone acetyltransferase activity. Mol Cancer Ther 2005; 4(10): 1521-32.
[http://dx.doi.org/10.1158/1535-7163.MCT-05-0135] [PMID: 16227401]
[57]
Gajer JM, Furdas SD, Gründer A, et al. Histone acetyltransferase inhibitors block neuroblastoma cell growth in vivo oncogenesis 2015.4e137
[http://dx.doi.org/10.1038/oncsis.2014.51] [PMID: 25664930]
[58]
Sangshetti JN, Sakle NS, Dehghan MHG, Shinde DB. Histone deacetylases as targets for multiple diseases. Mini Rev Med Chem 2013; 13(7): 1005-26.
[http://dx.doi.org/10.2174/1389557511313070006] [PMID: 22876951]
[59]
Haigis MC, Guarente LP. Mammalian sirtuins--emerging roles in physiology, aging, and calorie restriction. Genes Dev 2006; 20(21): 2913-21.
[http://dx.doi.org/10.1101/gad.1467506] [PMID: 17079682]
[60]
Yoshida M, Kijima M, Akita M, Beppu T. Potent and specific inhibition of mammalian histone deacetylase both in vivo and in vitro by trichostatin A. J Biol Chem 1990; 265(28): 17174-9.
[PMID: 2211619]
[61]
Mann BS, Johnson JR, Cohen MH, Justice R, Pazdur R. FDA approval summary: vorinostat for treatment of advanced primary cutaneous T-cell lymphoma. Oncologist 2007; 12(10): 1247-52.
[http://dx.doi.org/10.1634/theoncologist.12-10-1247] [PMID: 17962618]
[62]
Manal M, Chandrasekar MJN, Gomathi Priya J, Nanjan MJ. Inhibitors of histone deacetylase as antitumor agents: A critical review. Bioorg Chem 2016; 67: 18-42.
[http://dx.doi.org/10.1016/j.bioorg.2016.05.005] [PMID: 27239721]
[63]
Eckschlager T, Plch J, Stiborova M, Hrabeta J. Histone Deacetylase Inhibitors as Anticancer Drugs. Int J Mol Sci 2017; 18(7)E1414
[http://dx.doi.org/10.3390/ijms18071414] [PMID: 28671573]
[64]
Smith EM, Walker BA, Davenport EL, Aronson LI, Krige D, Hooftman L, et al. Inhibition of HDACs and Aminopeptidases Is Highly Synergistic in Myeloma Cells Resulting in Cell Death Via the Upregulation of BIRC3, a Key Mediator of NF-KappaB Signalling. Blood 2009; 114(22): 251-2.
[http://dx.doi.org/10.1182/blood.V114.22.607.607]
[65]
Haggarty SJ, Koeller KM, Wong JC, Grozinger CM, Schreiber SL. Domain-selective small-molecule inhibitor of histone deacetylase 6 (HDAC6)-mediated tubulin deacetylation. Proc Natl Acad Sci USA 2003; 100(8): 4389-94.
[http://dx.doi.org/10.1073/pnas.0430973100] [PMID: 12677000]
[66]
Butler KV, Kalin J, Brochier C, Vistoli G, Langley B, Kozikowski AP. Rational design and simple chemistry yield a superior, neuroprotective HDAC6 inhibitor, tubastatin A. J Am Chem Soc 2010; 132(31): 10842-6.
[http://dx.doi.org/10.1021/ja102758v] [PMID: 20614936]
[67]
King K, Hauser AT, Melesina J, Sippl W, Jung M. Carbamates as Potential Prodrugs and a New Warhead for HDAC Inhibition. Molecules 2018; 23(2)E321
[http://dx.doi.org/10.3390/molecules23020321] [PMID: 29393896]
[68]
Riggs MG, Whittaker RG, Neumann JR, Ingram VM. n-Butyrate causes histone modification in HeLa and Friend erythroleukaemia cells. Nature 1977; 268(5619): 462-4.
[http://dx.doi.org/10.1038/268462a0] [PMID: 268489]
[69]
Newmark HL, Young CW. Butyrate and phenylacetate as differentiating agents: practical problems and opportunities. J Cell Biochem Suppl 1995; 22: 247-53.
[http://dx.doi.org/10.1002/jcb.240590831] [PMID: 8538206]
[70]
Gaschott T, Maassen CU, Stein J. Tributyrin, a butyrate precursor, impairs growth and induces apoptosis and differentiation in pancreatic cancer cells. Anticancer Res 2001; 21(4A): 2815-9.
[PMID: 11724360]
[71]
Vinolo MAR, Rodrigues HG, Hatanaka E, Sato FT, Sampaio SC, Curi R. Suppressive effect of short-chain fatty acids on production of proinflammatory mediators by neutrophils. J Nutr Biochem 2011; 22(9): 849-55.
[http://dx.doi.org/10.1016/j.jnutbio.2010.07.009] [PMID: 21167700]
[72]
Engelhard HH, Homer RJ, Duncan HA, Rozental J. Inhibitory effects of phenylbutyrate on the proliferation, morphology, migration and invasiveness of malignant glioma cells. J Neurooncol 1998; 37(2): 97-108.
[http://dx.doi.org/10.1023/A:1005865125588] [PMID: 9524087]
[73]
Carducci M, Bowling MK, Eisenberger M, Sinbaldi V, Chen TL, Noe D, et al. Phenylbutyrate (PB) for refractory solid tumors: Phase I evaluation of continuous oral PB exposure. Proceedings of the American Association for Cancer Research Annual Meeting. 39: 507.
[74]
Michaelis M, Doerr HW, Cinatl J Jr. Valproic acid as anti-cancer drug. Curr Pharm Des 2007; 13(33): 3378-93.
[http://dx.doi.org/10.2174/138161207782360528] [PMID: 18045192]
[75]
Prakash S, Foster BJ, Meyer M, et al. Chronic oral administration of CI-994: a phase 1 study. Invest New Drugs 2001; 19(1): 1-11.
[http://dx.doi.org/10.1023/A:1006489328324] [PMID: 11291827]
[76]
von Tresckow B, Sayehli C, Aulitzky WE, et al. Phase I study of domatinostat (4SC-202), a class I histone deacetylase inhibitor in patients with advanced hematological malignancies. Eur J Haematol 2019; 102(2): 163-73.
[http://dx.doi.org/10.1111/ejh.13188] [PMID: 30347469]
[77]
Saito A, Yamashita T, Mariko Y, et al. A synthetic inhibitor of histone deacetylase, MS-27-275, with marked in vivo antitumor activity against human tumors. Proc Natl Acad Sci USA 1999; 96(8): 4592-7.
[http://dx.doi.org/10.1073/pnas.96.8.4592] [PMID: 10200307]
[78]
Witta SE, Jotte RM, Konduri K, et al. Randomized phase II trial of erlotinib with and without entinostat in patients with advanced non-small-cell lung cancer who progressed on prior chemotherapy. J Clin Oncol 2012; 30(18): 2248-55.
[http://dx.doi.org/10.1200/JCO.2011.38.9411] [PMID: 22508830]
[79]
Boumber Y, Younes A, Garcia-Manero G. Mocetinostat (MGCD0103): a review of an isotype-specific histone deacetylase inhibitor. Expert Opin Investig Drugs 2011; 20(6): 823-9.
[http://dx.doi.org/10.1517/13543784.2011.577737] [PMID: 21554162]
[80]
Batlevi CL, Crump M, Andreadis C, et al. A phase 2 study of mocetinostat, a histone deacetylase inhibitor, in relapsed or refractory lymphoma. Br J Haematol 2017; 178(3): 434-41.
[http://dx.doi.org/10.1111/bjh.14698] [PMID: 28440559]
[81]
Manero GG, Selina L, Virginia K, Maureen C, Besa EC, Rossetti JM, et al. Combination Therapy With Mocetinostat, An Oral, Spectrum-Selective Histone Deacetylase (HDAC) Inhibitor, and 5-Azaciditine: Indication Of Clinical Activity In MDS. Blood 2013; 122(21)
[http://dx.doi.org/10.1182/blood.V122.21.1550.1550]
[82]
Luger SM, O’Connell CL, Klimek V, Cooper MA, Besa EC, Rossetti JM, et al. A phase II study of mocetinostat, an oral isotype-selective histone deacetylase (HDAC) inhibitor, in combination with 5-azacitidine in patients with myelodysplastic syndrome (MDS). J Clin Oncol 2013; 31(15)
[83]
Furumai R, Matsuyama A, Kobashi N, et al. FK228 (depsipeptide) as a natural prodrug that inhibits class I histone deacetylases. Cancer Res 2002; 62(17): 4916-21.
[PMID: 12208741]
[84]
VanderMolen KM, McCulloch W, Pearce CJ, Oberlies NH. Romidepsin (Istodax, NSC 630176, FR901228, FK228, depsipeptide): a natural product recently approved for cutaneous T-cell lymphoma. J Antibiot (Tokyo) 2011; 64(8): 525-31.
[http://dx.doi.org/10.1038/ja.2011.35] [PMID: 21587264]
[85]
Barbarotta L, Hurley K. Romidepsin for the Treatment of Peripheral T-Cell Lymphoma. J Adv Pract Oncol 2015; 6(1): 22-36.
[PMID: 26413372]
[86]
Kozako T, Suzuki T, Yoshimitsu M, Arima N, Honda S, Soeda S. Anticancer agents targeted to sirtuins. Molecules 2014; 19(12): 20295-313.
[http://dx.doi.org/10.3390/molecules191220295] [PMID: 25486244]
[87]
Lavu S, Boss O, Elliott PJ, Lambert PD. Sirtuins--novel therapeutic targets to treat age-associated diseases. Nat Rev Drug Discov 2008; 7(10): 841-53.
[http://dx.doi.org/10.1038/nrd2665] [PMID: 18827827]
[88]
Singh PK. Histone methyl transferases: A class of epigenetic opportunities to counter uncontrolled cell proliferation. Eur J Med Chem 2019; 166: 351-68.
[http://dx.doi.org/10.1016/j.ejmech.2019.01.069] [PMID: 30735901]
[89]
Barski A, Cuddapah S, Cui K, et al. High-resolution profiling of histone methylations in the human genome. Cell 2007; 129(4): 823-37.
[http://dx.doi.org/10.1016/j.cell.2007.05.009] [PMID: 17512414]
[90]
Li X, Wang C, Jiang H, Luo C. A patent review of arginine methyltransferase inhibitors (2010-2018). Expert Opin Ther Pat 2019; 29(2): 97-114.
[http://dx.doi.org/10.1080/13543776.2019.1567711] [PMID: 30640571]
[91]
Zhou S-h, Sun P-j, Zhao Y-q, Zhang Y, Yu N-f. Research progress of DOT1L inhibitors in cancer. Yao Xue Xue Bao 2018; 53(4): 500-8.
[92]
McLean CM, Karemaker ID, van Leeuwen F. The emerging roles of DOT1L in leukemia and normal development. Leukemia 2014; 28(11): 2131-8.
[http://dx.doi.org/10.1038/leu.2014.169] [PMID: 24854991]
[93]
Daigle SR, Olhava EJ, Therkelsen CA, et al. Selective killing of mixed lineage leukemia cells by a potent small-molecule DOT1L inhibitor. Cancer Cell 2011; 20(1): 53-65.
[http://dx.doi.org/10.1016/j.ccr.2011.06.009] [PMID: 21741596]
[94]
Daigle SR, Olhava EJ, Therkelsen CA, et al. Potent inhibition of DOT1L as treatment of MLL-fusion leukemia. Blood 2013; 122(6): 1017-25.
[http://dx.doi.org/10.1182/blood-2013-04-497644] [PMID: 23801631]
[95]
Chen J, Park HJ. Computer-Aided Discovery of Massonianoside B as a Novel Selective DOT1L Inhibitor. ACS Chem Biol 2019; 14(5): 873-81.
[http://dx.doi.org/10.1021/acschembio.8b00933] [PMID: 30951287]
[96]
Yan KS, Lin CY, Liao TW, et al. EZH2 in Cancer Progression and Potential Application in Cancer Therapy: A Friend or Foe? Int J Mol Sci 2017; 18(6)E1172
[http://dx.doi.org/10.3390/ijms18061172] [PMID: 28561778]
[97]
Ernst T, Chase AJ, Score J, et al. Inactivating mutations of the histone methyltransferase gene EZH2 in myeloid disorders. Nat Genet 2010; 42(8): 722-6.
[http://dx.doi.org/10.1038/ng.621] [PMID: 20601953]
[98]
Girard N, Bazille C, Lhuissier E, et al. 3-Deazaneplanocin A (DZNep), an inhibitor of the histone methyltransferase EZH2, induces apoptosis and reduces cell migration in chondrosarcoma cells. PLoS One 2014; 9(5)e98176
[http://dx.doi.org/10.1371/journal.pone.0098176] [PMID: 24852755]
[99]
Fiskus W, Wang Y, Sreekumar A, et al. Combined epigenetic therapy with the histone methyltransferase EZH2 inhibitor 3-deazaneplanocin A and the histone deacetylase inhibitor panobinostat against human AML cells. Blood 2009; 114(13): 2733-43.
[http://dx.doi.org/10.1182/blood-2009-03-213496] [PMID: 19638619]
[100]
Knutson SK, Wigle TJ, Warholic NM, et al. A selective inhibitor of EZH2 blocks H3K27 methylation and kills mutant lymphoma cells. Nat Chem Biol 2012; 8(11): 890-6.
[http://dx.doi.org/10.1038/nchembio.1084] [PMID: 23023262]
[101]
McCabe MT, Ott HM, Ganji G, et al. EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations. Nature 2012; 492(7427): 108-12.
[http://dx.doi.org/10.1038/nature11606] [PMID: 23051747]
[102]
Knutson SK, Kawano S, Minoshima Y, et al. Selective inhibition of EZH2 by EPZ-6438 leads to potent antitumor activity in EZH2-mutant non-Hodgkin lymphoma. Mol Cancer Ther 2014; 13(4): 842-54.
[http://dx.doi.org/10.1158/1535-7163.MCT-13-0773] [PMID: 24563539]
[103]
Kurmasheva RT, Sammons M, Favours E, et al. Initial testing (stage 1) of tazemetostat (EPZ-6438), a novel EZH2 inhibitor, by the Pediatric Preclinical Testing Program. Pediatr Blood Cancer 2017; 64(3)
[http://dx.doi.org/10.1002/pbc.26218] [PMID: 27555605]
[104]
Mayr C, Helm K, Jakab M, et al. The histone methyltransferase G9a: a new therapeutic target in biliary tract cancer. Hum Pathol 2018; 72: 117-26.
[http://dx.doi.org/10.1016/j.humpath.2017.11.003] [PMID: 29133140]
[105]
Kubicek S, O’Sullivan RJ, August EM, et al. Reversal of H3K9me2 by a small-molecule inhibitor for the G9a histone methyltransferase. Mol Cell 2007; 25(3): 473-81.
[http://dx.doi.org/10.1016/j.molcel.2007.01.017] [PMID: 17289593]
[106]
Pappano WN, Guo J, He Y, et al. The Histone Methyltransferase Inhibitor A-366 Uncovers a Role for G9a/GLP in the Epigenetics of Leukemia. PLoS One 2015; 10(7)e0131716
[http://dx.doi.org/10.1371/journal.pone.0131716] [PMID: 26147105]
[107]
Spellmon N, Holcomb J, Trescott L, Sirinupong N, Yang Z. Structure and function of SET and MYND domain-containing proteins. Int J Mol Sci 2015; 16(1): 1406-28.
[http://dx.doi.org/10.3390/ijms16011406] [PMID: 25580534]
[108]
Hamamoto R, Furukawa Y, Morita M, et al. SMYD3 encodes a histone methyltransferase involved in the proliferation of cancer cells. Nat Cell Biol 2004; 6(8): 731-40.
[http://dx.doi.org/10.1038/ncb1151] [PMID: 15235609]
[109]
Hu L, Zhu YT, Qi C, Zhu Y-J. Identification of Smyd4 as a potential tumor suppressor gene involved in breast cancer development. Cancer Res 2009; 69(9): 4067-72.
[http://dx.doi.org/10.1158/0008-5472.CAN-08-4097] [PMID: 19383909]
[110]
Nguyen H, Allali-Hassani A, Antonysamy S, et al. LLY-507, a Cell-active, Potent, and Selective Inhibitor of Protein-lysine Methyltransferase SMYD2. J Biol Chem 2015; 290(22): 13641-53.
[http://dx.doi.org/10.1074/jbc.M114.626861] [PMID: 25825497]
[111]
Ferguson AD, Larsen NA, Howard T, et al. Structural basis of substrate methylation and inhibition of SMYD2. Structure 2011; 19(9): 1262-73.
[http://dx.doi.org/10.1016/j.str.2011.06.011] [PMID: 21782458]
[112]
Sweis RF, Wang Z, Algire M, et al. Discovery of A-893, A New Cell-Active Benzoxazinone Inhibitor of Lysine Methyltransferase SMYD2. ACS Med Chem Lett 2015; 6(6): 695-700.
[http://dx.doi.org/10.1021/acsmedchemlett.5b00124] [PMID: 26101576]
[113]
Stouth DW, vanLieshout TL, Shen NY, Ljubicic V. Regulation of Skeletal Muscle Plasticity by Protein Arginine Methyltransferases and Their Potential Roles in Neuromuscular Disorders. Front Physiol 2017; 8: 870.
[http://dx.doi.org/10.3389/fphys.2017.00870] [PMID: 29163212]
[114]
Yao R, Jiang H, Ma Y, et al. PRMT7 induces epithelial-to-mesenchymal transition and promotes metastasis in breast cancer. Cancer Res 2014; 74(19): 5656-67.
[http://dx.doi.org/10.1158/0008-5472.CAN-14-0800] [PMID: 25136067]
[115]
Yang Y, Bedford MT. Protein arginine methyltransferases and cancer. Nat Rev Cancer 2013; 13(1): 37-50.
[http://dx.doi.org/10.1038/nrc3409] [PMID: 23235912]
[116]
Fedoriw A, Rajapurkar SR, O’Brien S, et al. Anti-tumor Activity of the Type I PRMT Inhibitor, GSK3368715, Synergizes with PRMT5 Inhibition through MTAP Loss. Cancer Cell 2019; 36(1): 100-114.e25.
[http://dx.doi.org/10.1016/j.ccell.2019.05.014] [PMID: 31257072]
[117]
Rasco D, Tolcher A, Siu LL, Heinhuis K, Postel-Vinay S, Barbash O, et al. A phase I, open-label, dose-escalation study to investigate the safety, pharmacokinetics, pharmacodynamics, and clinical activity of GSK3326595 in subjects with solid tumors and non-Hodgkin’s lymphoma. Cancer Res 2017; 77
[118]
Guccione E, Richard S. The regulation, functions and clinical relevance of arginine methylation. Nat Rev Mol Cell Biol 2019; 20(10): 642-57.
[http://dx.doi.org/10.1038/s41580-019-0155-x] [PMID: 31350521]
[119]
Metzger E, Wissmann M, Yin N, et al. LSD1 demethylates repressive histone marks to promote androgen-receptor-dependent transcription. Nature 2005; 437(7057): 436-9.
[http://dx.doi.org/10.1038/nature04020] [PMID: 16079795]
[120]
Zheng YC, Yu B, Jiang GZ, et al. Irreversible LSD1 Inhibitors: Application of Tranylcypromine and Its Derivatives in Cancer Treatment. Curr Top Med Chem 2016; 16(19): 2179-88.
[http://dx.doi.org/10.2174/1568026616666160216154042] [PMID: 26881714]
[121]
Sugino N, Kawahara M, Tatsumi G, et al. A novel LSD1 inhibitor NCD38 ameliorates MDS-related leukemia with complex karyotype by attenuating leukemia programs via activating super-enhancers. Leukemia 2017; 31(11): 2303-14.
[http://dx.doi.org/10.1038/leu.2017.59] [PMID: 28210006]
[122]
Hamm S, Kronthaler K, Parnitzke U, Prenzel T, Kohlhof H, Vitt D. A novel LSD1/HDAC inhibitor 4SC-202 inhibits immunosuppressive MDSC and enhances immunogenicity of tumor cells by up-regulation of TAA expression. European Journal of Cancer 2016; 55S21
[123]
Wen H, Li G, Chen Y, et al. A specific assay for JmjC domain-containing lysine demethylase and its application to inhibitor screening. Sci China Life Sci 2019; 62(10): 1404-8.
[http://dx.doi.org/10.1007/s11427-019-9582-9] [PMID: 31502087]
[124]
Hamada S, Kim T-D, Suzuki T, et al. Synthesis and activity of N-oxalylglycine and its derivatives as Jumonji C-domain-containing histone lysine demethylase inhibitors. Bioorg Med Chem Lett 2009; 19(10): 2852-5.
[http://dx.doi.org/10.1016/j.bmcl.2009.03.098] [PMID: 19359167]
[125]
Hopkinson RJ, Tumber A, Yapp C, et al. 5-Carboxy-8-hydroxyquinoline is a broad spectrum 2-oxoglutarate oxygenase inhibitor which causes iron translocation. Chem Sci (Camb) 2013; 4(8): 3110-7.
[http://dx.doi.org/10.1039/c3sc51122g] [PMID: 26682036]
[126]
Raeisossadati R, Móvio MI, Walter LT, Takada SH, Del Debbio CB, Kihara AH. Small Molecule GSK-J1 Affects Differentiation of Specific Neuronal Subtypes in Developing Rat Retina. Mol Neurobiol 2019; 56(3): 1972-83.
[http://dx.doi.org/10.1007/s12035-018-1197-3] [PMID: 29981055]
[127]
Abdelfatah E, Kerner Z, Nanda N, Ahuja N. Epigenetic therapy in gastrointestinal cancer: the right combination. Therap Adv Gastroenterol 2016; 9(4): 560-79.
[http://dx.doi.org/10.1177/1756283X16644247] [PMID: 27366224]
[128]
Kaminskas E, Farrell AT, Wang YC, Sridhara R, Pazdur R. FDA drug approval summary: azacitidine (5-azacytidine, Vidaza) for injectable suspension. Oncologist 2005; 10(3): 176-82.
[http://dx.doi.org/10.1634/theoncologist.10-3-176] [PMID: 15793220]
[129]
Tsai HC, Li H, Van Neste L, et al. Transient low doses of DNA-demethylating agents exert durable antitumor effects on hematological and epithelial tumor cells. Cancer Cell 2012; 21(3): 430-46.
[http://dx.doi.org/10.1016/j.ccr.2011.12.029] [PMID: 22439938]
[130]
Liu Z, Gao Y, Li X. Cancer epigenetics and the potential of epigenetic drugs for treating solid tumors. Expert Rev Anticancer Ther 2019; 19(2): 139-49.
[http://dx.doi.org/10.1080/14737140.2019.1552139] [PMID: 30470148]
[131]
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(1): 103-7.
[http://dx.doi.org/10.1038/5047] [PMID: 9916800]
[132]
Klisovic MI, Maghraby EA, Parthun MR, et al. Depsipeptide (FR 901228) promotes histone acetylation, gene transcription, apoptosis and its activity is enhanced by DNA methyltransferase inhibitors in AML1/ETO-positive leukemic cells. Leukemia 2003; 17(2): 350-8.
[http://dx.doi.org/10.1038/sj.leu.2402776] [PMID: 12592335]
[133]
Walton TJ, Li G, Seth R, McArdle SE, Bishop MC, Rees RC. DNA demethylation and histone deacetylation inhibition co-operate to re-express estrogen receptor beta and induce apoptosis in prostate cancer cell-lines. Prostate 2008; 68(2): 210-22.
[http://dx.doi.org/10.1002/pros.20673] [PMID: 18092350]
[134]
Ecke I, Petry F, Rosenberger A, et al. Antitumor effects of a combined 5-aza-2'deoxycytidine and valproic acid treatment on rhabdomyosarcoma and medulloblastoma in Ptch mutant mice. Cancer Res 2009; 69(3): 887-95.
[http://dx.doi.org/10.1158/0008-5472.CAN-08-0946] [PMID: 19155313]
[135]
Garcia-Manero G, Kantarjian HM, Sanchez-Gonzalez B, et al. Phase 1/2 study of the combination of 5-aza-2′-deoxycytidine with valproic acid in patients with leukemia. Blood 2006; 108(10): 3271-9.
[http://dx.doi.org/10.1182/blood-2006-03-009142] [PMID: 16882711]
[136]
Takashina T, Kinoshita I, Kikuchi J, et al. Combined inhibition of EZH2 and histone deacetylases as a potential epigenetic therapy for non-small-cell lung cancer cells. Cancer Sci 2016; 107(7): 955-62.
[http://dx.doi.org/10.1111/cas.12957] [PMID: 27116120]
[137]
Glasspool RM, Teodoridis JM, Brown R. Epigenetics as a mechanism driving polygenic clinical drug resistance. Br J Cancer 2006; 94(8): 1087-92.
[http://dx.doi.org/10.1038/sj.bjc.6603024] [PMID: 16495912]
[138]
Juergens RA, Wrangle J, Vendetti FP, et al. Combination epigenetic therapy has efficacy in patients with refractory advanced non-small cell lung cancer. Cancer Discov 2011; 1(7): 598-607.
[http://dx.doi.org/10.1158/2159-8290.CD-11-0214] [PMID: 22586682]
[139]
Momparler RL, Ayoub J. Potential of 5-aza-2′-deoxycytidine (Decitabine) a potent inhibitor of DNA methylation for therapy of advanced non-small cell lung cancer. Lung Cancer 2001; 34(Suppl. 4): S111-5.
[http://dx.doi.org/10.1016/S0169-5002(01)00397-X] [PMID: 11742714]
[140]
Morita S, Iida S, Kato K, Takagi Y, Uetake H, Sugihara K. The synergistic effect of 5-aza-2′-deoxycytidine and 5-fluorouracil on drug-resistant tumors. Oncology 2006; 71(5-6): 437-45.
[http://dx.doi.org/10.1159/000107110] [PMID: 17690560]
[141]
Plumb JA, Strathdee G, Sludden J, Kaye SB, Brown R. Reversal of drug resistance in human tumor xenografts by 2′-deoxy-5-azacytidine-induced demethylation of the hMLH1 gene promoter. Cancer Res 2000; 60(21): 6039-44.
[PMID: 11085525]
[142]
Crea F, Giovannetti E, Cortesi F, et al. Epigenetic mechanisms of irinotecan sensitivity in colorectal cancer cell lines. Mol Cancer Ther 2009; 8(7): 1964-73.
[http://dx.doi.org/10.1158/1535-7163.MCT-09-0027] [PMID: 19531575]
[143]
Wu J, Hu CP, Gu QH, Li YP, Song M. Trichostatin A sensitizes cisplatin-resistant A549 cells to apoptosis by up-regulating death-associated protein kinase. Acta Pharmacol Sin 2010; 31(1): 93-101.
[http://dx.doi.org/10.1038/aps.2009.183] [PMID: 20048748]
[144]
Hermann F. Clinical development of 4SC-202, a combined epigenetic inhibitor of HDAC class I and LSD1, to overcome anti-PD-1 refractoriness and increase efficacy of checkpoint inhibition. J Clin Oncol 2017; 35.
[http://dx.doi.org/10.1200/JCO.2017.35.15_suppl.e14096]
[145]
Zhang K, Wang J, Tong TR, et al. Loss of H2B monoubiquitination is associated with poor-differentiation and enhanced malignancy of lung adenocarcinoma. Int J Cancer 2017; 141(4): 766-77.
[http://dx.doi.org/10.1002/ijc.30769] [PMID: 28481029]
[146]
Li Y, Xu Z, Li B, et al. Epigenetic silencing of miRNA-9 is correlated with promoter-proximal CpG island hypermethylation in gastric cancer in vitro and in vivo. Int J Oncol 2014; 45(6): 2576-86.
[http://dx.doi.org/10.3892/ijo.2014.2667] [PMID: 25270964]
[147]
Bandres E, Agirre X, Bitarte N, et al. Epigenetic regulation of microRNA expression in colorectal cancer. Int J Cancer 2009; 125(11): 2737-43.
[http://dx.doi.org/10.1002/ijc.24638] [PMID: 19521961]
[148]
Kang H-W, Crawford M, Fabbri M, et al. A mathematical model for microRNA in lung cancer. PLoS One 2013; 8(1)e53663
[http://dx.doi.org/10.1371/journal.pone.0053663] [PMID: 23365639]
[149]
Lu Y-C, Cheng A-J. MicroRNA profiling in head and neck cancer. Cancer Res 2010; 70.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy