Login Register Cart 0
Generic placeholder image

Current Cancer Drug Targets

Editor-in-Chief

ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in Chinese
Review Article

Epigenetics in Metastatic Breast Cancer: Its Regulation and Implications in Diagnosis, Prognosis and Therapeutics

Author(s): Yuan Seng Wu, Zhong Yang Lee, Lay-Hong Chuah, Chun Wai Mai and Siew Ching Ngai*

Volume 19, Issue 2, 2019

Page: [82 - 100] Pages: 19

DOI: 10.2174/1568009618666180430130248

Price: $65

Abstract

Despite advances in the treatment regimen, the high incidence rate of breast cancer (BC) deaths is mostly caused by metastasis. Recently, the aberrant epigenetic modifications, which involve DNA methylation, histone modifications and microRNA (miRNA) regulations become attractive targets to treat metastatic breast cancer (MBC). In this review, the epigenetic alterations of DNA methylation, histone modifications and miRNA regulations in regulating MBC are discussed. The preclinical and clinical trials of epigenetic drugs such as the inhibitor of DNA methyltransferase (DNMTi) and the inhibitor of histone deacetylase (HDACi), as a single or combined regimen with other epigenetic drug or standard chemotherapy drug to treat MBCs are discussed. The combined regimen of epigenetic drugs or with standard chemotherapy drugs enhance the therapeutic effect against MBC. Evidences that epigenetic changes could have implications in diagnosis, prognosis and therapeutics for MBC are also presented. Several genes have been identified as potential epigenetic biomarkers for diagnosis and prognosis, as well as therapeutic targets for MBC. Endeavors in clinical trials of epigenetic drugs against MBC should be continued although limited success has been achieved. Future discovery of epigenetic drugs from natural resources would be an attractive natural treatment regimen for MBC. Further research is warranted in translating research into clinical practice with the ultimate goal of treating MBC by epigenetic therapy in the near future.

Keywords: Breast cancer, metastasis, epigenetic therapy, DNA methylation, histone deacetylation, microRNA regulations, epigenetic biomarker.

« Previous Next »
Graphical Abstract

[1]
Dedeurwaerder, S.; Fumagalli, D.; Fuks, F. Unravelling the epigenomic dimension of breast cancers. Curr. Opin. Oncol., 2011, 23(6), 559-565.
[2]
Huynh, K.T.; Chong, K.K.; Greenberg, E.S.; Hoon, D.S. Epigenetics of estrogen receptor-negative primary breast cancer. Expert Rev. Mol. Diagn., 2012, 12(4), 371-382.
[3]
Eccles, S.A.; Welch, D.R. Metastasis: recent discoveries and novel treatment strategies. Lancet, 2007, 369(9574), 1742-1757.
[4]
Gupta, G.P. Massague, J. Cancer metastasis: building a framework. Cell, 2006, 127(4), 679-695.
[5]
Balic, M.; Schwarzenbacher, D.; Stanzer, S.; Heitzer, E.; Auer, M.; Geigl, J.B.; Cote, R.J.; Datar, R.H.; Dandachi, N. Genetic and epigenetic analysis of putative breast cancer stem cell models. BMC Cancer, 2013, 13, 358.
[6]
Taby, R.; Issa, J.P. Cancer epigenetics. CA Cancer J. Clin., 2010, 60(6), 376-392.
[7]
Lustberg, M.B.; Ramaswamy, B. Epigenetic targeting in breast cancer: therapeutic impact and future direction. Drug News Perspect., 2009, 22(7), 369-381.
[8]
Cai, F.F.; Kohler, C.; Zhang, B.; Wang, M.H.; Chen, W.J.; Zhong, X.Y. Epigenetic therapy for breast cancer. Int. J. Mol. Sci., 2011, 12(7), 4465-4487.
[9]
Jovanovic, J.; Ronneberg, J.A.; Tost, J.; Kristensen, V. The epigenetics of breast cancer. Mol. Oncol., 2010, 4(3), 242-254.
[10]
Strathdee, G. Epigenetic versus genetic alterations in the inactivation of E-cadherin. Semin. Cancer Biol., 2002, 12(5), 373-379.
[11]
Veeck, J.; Esteller, M. Breast cancer epigenetics: from DNA methylation to microRNAs. J. Mammary Gland Biol. Neoplasia, 2010, 15(1), 5-17.
[12]
Tang, Y.; Wang, Y.; Kiani, M.F.; Wang, B. Classification, Treatment Strategy, and Associated Drug Resistance in Breast Cancer. Clin. Breast Cancer, 2016, 16(5), 335-343.
[13]
Viale, G. The current state of breast cancer classification. Ann. Oncol., 2012, 23(Suppl. 10), x207-x210.
[14]
Hsiao, Y.H.; Chou, M.C.; Fowler, C.; Mason, J.T.; Man, Y.G. Breast cancer heterogeneity: mechanisms, proofs, and implications. J. Cancer, 2010, 1, 6-13.
[15]
Holliday, D.L.; Speirs, V. Choosing the right cell line for breast cancer research. Breast Cancer Res., 2011, 13(4), 215.
[16]
Byler, S.; Goldgar, S.; Heerboth, S.; Leary, M.; Housman, G.; Moulton, K.; Sarkar, S. Genetic and epigenetic aspects of breast cancer progression and therapy. Anticancer Res., 2014, 34(3), 1071-1077.
[17]
Sarkar, S.; Goldgar, S.; Byler, S.; Rosenthal, S.; Heerboth, S. Demethylation and re-expression of epigenetically silenced tumor suppressor genes: sensitization of cancer cells by combination therapy. Epigenomics, 2013, 5(1), 87-94.
[18]
Byler, S.; Sarkar, S. Do epigenetic drug treatments hold the key to killing cancer progenitor cells? Epigenomics, 2014, 6(2), 161-165.
[19]
Sarkar, S.; Horn, G.; Moulton, K.; Oza, A.; Byler, S.; Kokolus, S.; Longacre, M. Cancer development, progression, and therapy: an epigenetic overview. Int. J. Mol. Sci., 2013, 14(10), 21087-21113.
[20]
Tam, W.L.; Weinberg, R.A. The epigenetics of epithelial-mesenchymal plasticity in cancer. Nat. Med., 2013, 19(11), 1438-1449.
[21]
Nieto, M.A. Epithelial plasticity: a common theme in embryonic and cancer cells. Science, 2013, 342(6159), 1234850.
[22]
Singh, A.; Settleman, J. EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer. Oncogene, 2010, 29(34), 4741-4751.
[23]
Housman, G.; Byler, S.; Heerboth, S.; Lapinska, K.; Longacre, M.; Snyder, N.; Sarkar, S. Drug resistance in cancer: an overview. Cancers (Basel), 2014, 6(3), 1769-1792.
[24]
Heerboth, S.; Lapinska, K.; Snyder, N.; Leary, M.; Rollinson, S.; Sarkar, S. Use of epigenetic drugs in disease: an overview. Genet. Epigenet., 2014, 6, 9-19.
[25]
Lustberg, M.B.; Ramaswamy, B. Epigenetic therapy in breast cancer. Curr. Breast Cancer Rep., 2011, 3(1), 34-43.
[26]
Chik, F.; Szyf, M. Effects of specific DNMT gene depletion on cancer cell transformation and breast cancer cell invasion; toward selective DNMT inhibitors. Carcinogenesis, 2011, 32(2), 224-232.
[27]
Widschwendter, M.; Jones, P.A. DNA methylation and breast carcinogenesis. Oncogene, 2002, 21(35), 5462-5482.
[28]
Esteller, M. Cancer epigenomics: DNA methylomes and histone-modification maps. Nat. Rev. Genet., 2007, 8(4), 286-298.
[29]
Jones, P.A.; Baylin, S.B. The epigenomics of cancer. Cell, 2007, 128(4), 683-692.
[30]
Ehrlich, M. DNA methylation in cancer: too much, but also too little. Oncogene, 2002, 21(35), 5400-5413.
[31]
Eden, A.; Gaudet, F.; Waghmare, A.; Jaenisch, R. Chromosomal instability and tumors promoted by DNA hypomethylation. Science, 2003, 300(5618), 455.
[32]
Lo, P.K.; Sukumar, S. Epigenomics and breast cancer. Pharmacogenomics, 2008, 9(12), 1879-1902.
[33]
Yan, P.S.; Perry, M.R.; Laux, D.E.; Asare, A.L.; Caldwell, C.W.; Huang, T.H. CpG island arrays: an application toward deciphering epigenetic signatures of breast cancer. Clin. Cancer Res., 2000, 6(4), 1432-1438.
[34]
Bestor, T.H. The DNA methyltransferases of mammals. Hum. Mol. Genet., 2000, 9(16), 2395-2402.
[35]
Hatzimichael, E.; Crook, T. Cancer epigenetics: new therapies and new challenges. J. Drug Deliv., 2013, 2013, 529312.
[36]
Schaefer, M.; Hagemann, S.; Hanna, K.; Lyko, F. Azacytidine inhibits RNA methylation at DNMT2 target sites in human cancer cell lines. Cancer Res., 2009, 69(20), 8127-8132.
[37]
Giacinti, L.; Claudio, P.P.; Lopez, M.; Giordano, A. Epigenetic information and estrogen receptor alpha expression in breast cancer. Oncologist, 2006, 11(1), 1-8.
[38]
Li, E. Chromatin modification and epigenetic reprogramming in mammalian development. Nat. Rev. Genet., 2002, 3(9), 662-673.
[39]
Hoque, M.O.; Prencipe, M.; Poeta, M.L.; Barbano, R.; Valori, V.M.; Copetti, M.; Gallo, A.P.; Brait, M.; Maiello, E.; Apicella, A.; Rossiello, R.; Zito, F.; Stefania, T.; Paradiso, A.; Carella, M.; Dallapiccola, B.; Murgo, R.; Carosi, I.; Bisceglia, M.; Fazio, V.M.; Sidransky, D.; Parrella, P. Changes in CpG islands promoter methylation patterns during ductal breast carcinoma progression. Cancer Epidemiol. Biomarkers Prev., 2009, 18(10), 2694-2700.
[40]
Chimonidou, M.; Strati, A.; Tzitzira, A.; Sotiropoulou, G.; Malamos, N.; Georgoulias, V.; Lianidou, E.S. DNA methylation of tumor suppressor and metastasis suppressor genes in circulating tumor cells. Clin. Chem., 2011, 57(8), 1169-1177.
[41]
Kornberg, R.D.; Lorch, Y. Twenty-five years of the nucleosome, fundamental particle of the eukaryote chromosome. Cell, 1999, 98(3), 285-294.
[42]
Kouzarides, T. Chromatin modifications and their function. Cell, 2007, 128(4), 693-705.
[43]
Nowsheen, S.; Aziz, K.; Tran, P.T.; Gorgoulis, V.G.; Yang, E.S.; Georgakilas, A.G. Epigenetic inactivation of DNA repair in breast cancer. Cancer Lett., 2014, 342(2), 213-222.
[44]
Razin, A.; Cedar, H. Distribution of 5-methylcytosine in chromatin. Proc. Natl. Acad. Sci. USA, 1977, 74(7), 2725-2728.
[45]
Razin, A.; Szyf, M. DNA methylation patterns. Formation and function. Biochim. Biophys. Acta, 1984, 782(4), 331-342.
[46]
Zhang, Y.; Ng, H.H.; Erdjument-Bromage, H.; Tempst, P.; Bird, A.; Reinberg, D. Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation. Genes Dev., 1999, 13(15), 1924-1935.
[47]
Rauch, T.A.; Wu, X.; Zhong, X.; Riggs, A.D.; Pfeifer, G.P. A human B cell methylome at 100-base pair resolution. Proc. Natl. Acad. Sci. USA, 2009, 106(3), 671-678.
[48]
Wei, Y.; Xia, W.; Zhang, Z.; Liu, J.; Wang, H.; Adsay, N.V.; Albarracin, C.; Yu, D.; Abbruzzese, J.L.; Mills, G.B.; Bast, R.C., Jr; Hortobagyi, G.N.; Hung, M.C. Loss of trimethylation at lysine 27 of histone H3 is a predictor of poor outcome in breast, ovarian, and pancreatic cancers. Mol. Carcinog., 2008, 47(9), 701-706.
[49]
Vincent-Salomon, A.; Thiery, J.P. Host microenvironment in breast cancer development: epithelial-mesenchymal transition in breast cancer development. Breast Cancer Res., 2003, 5(2), 101-106.
[50]
Basse, C.; Arock, M. The increasing roles of epigenetics in breast cancer: Implications for pathogenicity, biomarkers, prevention and treatment. Int. J. Cancer, 2015, 137(12), 2785-2794.
[51]
Esquela-Kerscher, A.; Slack, F.J. Oncomirs-microRNAs with a role in cancer. Nat. Rev. Cancer, 2006, 6(4), 259-269.
[52]
Chen, K.; Rajewsky, N. The evolution of gene regulation by transcription factors and microRNAs. Nat. Rev. Genet., 2007, 8(2), 93-103.
[53]
Lin, S.; Gregory, R.I. MicroRNA biogenesis pathways in cancer. Nat. Rev. Cancer, 2015, 15(6), 321-333.
[54]
Lujambio, A.; Esteller, M. How epigenetics can explain human metastasis: A new role for microRNAs. Cell Cycle, 2009, 8(3), 377-382.
[55]
Radpour, R.; Barekati, Z.; Kohler, C.; Schumacher, M.M.; Grussenmeyer, T.; Jenoe, P.; Hartmann, N.; Moes, S.; Letzkus, M.; Bitzer, J.; Lefkovits, I.; Staedtler, F.; Zhong, X.Y. Integrated epigenetics of human breast cancer: synoptic investigation of targeted genes, microRNAs and proteins upon demethylation treatment. PLoS One, 2011, 6(11), e27355.
[56]
Bartel, D.P.; Chen, C.Z. Micromanagers of gene expression: the potentially widespread influence of metazoan microRNAs. Nat. Rev. Genet., 2004, 5(5), 396-400.
[57]
Volinia, S.; Galasso, M.; Sana, M.E.; Wise, T.F.; Palatini, J.; Huebner, K.; Croce, C.M. Breast cancer signatures for invasiveness and prognosis defined by deep sequencing of microRNA. Proc. Natl. Acad. Sci. USA, 2012, 109(8), 3024-3029.
[58]
Iorio, M.V.; Ferracin, M.; Liu, C.G.; Veronese, A.; Spizzo, R.; Sabbioni, S.; Magri, E.; Pedriali, M.; Fabbri, M.; Campiglio, M.; Menard, S.; Palazzo, J.P.; Rosenberg, A.; Musiani, P.; Volinia, S.; Nenci, I.; Calin, G.A.; Querzoli, P.; Negrini, M.; Croce, C.M. MicroRNA gene expression deregulation in human breast cancer. Cancer Res., 2005, 65(16), 7065-7070.
[59]
Mattiske, S.; Suetani, R.J.; Neilsen, P.M.; Callen, D.F. The oncogenic role of miR-155 in breast cancer. Cancer Epidemiol. Biomarkers Prev., 2012, 21(8), 1236-1243.
[60]
Zhu, S.; Wu, H.; Wu, F.; Nie, D.; Sheng, S.; Mo, Y.Y. MicroRNA-21 targets tumor suppressor genes in invasion and metastasis. Cell Res., 2008, 18(3), 350-359.
[61]
Dumont, N.; Tlsty, T.D. Reflections on miR-ing effects in metastasis. Cancer Cell, 2009, 16(1), 3-4.
[62]
Wang, L.; Li, L.; Guo, R.; Li, X.; Lu, Y.; Guan, X.; Gitau, S.C.; Xu, C.; Yang, B.; Shan, H. miR-101 promotes breast cancer cell apoptosis by targeting Janus kinase 2. Cell. Physiol. Biochem., 2014, 34(2), 413-422.
[63]
Liu, J.; Pang, Y.; Wang, H.; Li, Y.; Sun, X.; Xu, F.; Ren, H.; Liu, D. miR-101 inhibits the proliferation and migration of breast cancer cells via downregulating the expression of DNA methyltransferase 3a. Xibao Yu Fenzi Mianyixue Zazhi, 2016, 32(3), 299-303.
[64]
Luo, Q.; Li, X.; Gao, Y.; Long, Y.; Chen, L.; Huang, Y.; Fang, L. MiRNA-497 regulates cell growth and invasion by targeting cyclin E1 in breast cancer. Cancer Cell Int., 2013, 13(1), 95.
[65]
Pouliot, M.C.; Labrie, Y.; Diorio, C.; Durocher, F. The role of methylation in breast cancer susceptibility and treatment. Anticancer Res., 2015, 35(9), 4569-4574.
[66]
Krawczyk, B.; Fabianowska-Majewska, K. Alteration of DNA methylation status in K562 and MCF-7 cancer cell lines by nucleoside analogues. Nucleosides Nucleotides Nucleic Acids, 2006, 25(9-11), 1029-1032.
[67]
Lyko, F.; Brown, R. DNA methyltransferase inhibitors and the development of epigenetic cancer therapies. J. Natl. Cancer Inst., 2005, 97(20), 1498-1506.
[68]
Szyf, M. Epigenetics, DNA methylation, and chromatin modifying drugs. Annu. Rev. Pharmacol. Toxicol., 2009, 49, 243-263.
[69]
Christman, J.K. 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.
[70]
Yoshiura, K.; Kanai, Y.; Ochiai, A.; Shimoyama, Y.; Sugimura, T.; Hirohashi, S. Silencing of the E-cadherin invasion-suppressor gene by CpG methylation in human carcinomas. Proc. Natl. Acad. Sci. USA, 1995, 92(16), 7416-7419.
[71]
Bandyopadhyay, S.; Pai, S.K.; Hirota, S.; Hosobe, S.; Takano, Y.; Saito, K.; Piquemal, D.; Commes, T.; Watabe, M.; Gross, S.C.; Wang, Y.; Ran, S.; Watabe, K. Role of the putative tumor metastasis suppressor gene Drg-1 in breast cancer progression. Oncogene, 2004, 23(33), 5675-5681.
[72]
Kuo, H.K.; Griffith, J.D.; Kreuzer, K.N. 5-Azacytidine induced methyltransferase-DNA adducts block DNA replication in vivo. Cancer Res., 2007, 67(17), 8248-8254.
[73]
Bauman, J.; Verschraegen, C.; Belinsky, S.; Muller, C.; Rutledge, T.; Fekrazad, M.; Ravindranathan, M.; Lee, S.J.; Jones, D. A phase I study of 5-azacytidine and erlotinib in advanced solid tumor malignancies. Cancer Chemother. Pharmacol., 2012, 69(2), 547-554.
[74]
Momparler, R.L. Epigenetic therapy of cancer with 5-aza-2′-deoxycytidine (decitabine). Semin. Oncol., 2005, 32(5), 443-451.
[75]
Qiu, X.; Qiao, F.; Su, X.; Zhao, Z.; Fan, H. Epigenetic activation of E-cadherin is a candidate therapeutic target in human hepatocellular carcinoma. Exp. Ther. Med., 2010, 1(3), 519-523.
[76]
Borges, S.; Doppler, H.; Perez, E.A.; Andorfer, C.A.; Sun, Z.; Anastasiadis, P.Z.; Thompson, E.; Geiger, X.J.; Storz, P. Pharmacologic reversion of epigenetic silencing of the PRKD1 promoter blocks breast tumor cell invasion and metastasis. Breast Cancer Res., 2013, 15(2), R66.
[77]
Xu, J.; Zhou, J-Y.; Tainsky, M.A.; Wu, G.S. Evidence that tumor necrosis factor–related apoptosis-inducing ligand induction by 5-aza-2′-deoxycytidine sensitizes human breast cancer cells to adriamycin. Cancer Res., 2007, 67(3), 1203-1211.
[78]
Mirza, S.; Sharma, G.; Pandya, P.; Ralhan, R. Demethylating agent 5-aza-2-deoxycytidine enhances susceptibility of breast cancer cells to anticancer agents. Mol. Cell. Biochem., 2010, 342(1-2), 101-109.
[79]
Appleton, K.; Mackay, H.J.; Judson, I.; Plumb, J.A.; McCormick, C.; Strathdee, G.; Lee, C.; Barrett, S.; Reade, S.; Jadayel, D.; Tang, A.; Bellenger, K.; Mackay, L.; Setanoians, A.; Schatzlein, A.; Twelves, C.; Kaye, S.B.; Brown, R. Phase I and pharmacodynamic trial of the DNA methyltransferase inhibitor decitabine and carboplatin in solid tumors. J. Clin. Oncol., 2007, 25(29), 4603-4609.
[80]
Chen, M.; Shabashvili, D.; Nawab, A.; Yang, S.X.; Dyer, L.M.; Brown, K.D.; Hollingshead, M.; Hunter, K.W.; Kaye, F.J.; Hochwald, S.N.; Marquez, V.E.; Steeg, P.; Zajac-Kaye, M. DNA methyltransferase inhibitor, zebularine, delays tumor growth and induces apoptosis in a genetically engineered mouse model of breast cancer. Mol. Cancer Ther., 2012, 11(2), 370-382.
[81]
Cheng, J.C.; Yoo, C.B.; Weisenberger, D.J.; Chuang, J.; Wozniak, C.; Liang, G.; Marquez, V.E.; Greer, S.; Orntoft, T.F.; Thykjaer, T.; Jones, P.A. Preferential response of cancer cells to zebularine. Cancer Cell, 2004, 6(2), 151-158.
[82]
Billam, M.; Sobolewski, M.D.; Davidson, N.E. Effects of a novel DNA methyltransferase inhibitor zebularine on human breast cancer cells. Breast Cancer Res. Treat., 2010, 120(3), 581-592.
[83]
Moyers, S.B.; Kumar, N.B. Green tea polyphenols and cancer chemoprevention: multiple mechanisms and endpoints for phase II trials. Nutr. Rev., 2004, 62(5), 204-211.
[84]
Inoue, M.; Tajima, K.; Mizutani, M.; Iwata, H.; Iwase, T.; Miura, S.; Hirose, K.; Hamajima, N.; Tominaga, S. Regular consumption of green tea and the risk of breast cancer recurrence: follow-up study from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC), Japan. Cancer Lett., 2001, 167(2), 175-182.
[85]
Singh, B.N.; Shankar, S.; Srivastava, R.K. Green tea catechin, epigallocatechin-3-gallate (EGCG): mechanisms, perspectives and clinical applications. Biochem. Pharmacol., 2011, 82(12), 1807-1821.
[86]
Hong, O.Y.; Noh, E.M.; Jang, H.Y.; Lee, Y.R.; Lee, B.K.; Jung, S.H.; Kim, J.S.; Youn, H.J. Epigallocatechin gallate inhibits the growth of MDA-MB-231 breast cancer cells via inactivation of the beta-catenin signaling pathway. Oncol. Lett., 2017, 14(1), 441-446.
[87]
Meeran, S.M.; Patel, S.N.; Chan, T-H.; Tollefsbol, T.O. A novel prodrug of epigallocatechin-3-gallate: differential epigenetic htert repression in human breast cancer cells. Cancer Prev. Res., 2011, 4(8), 1243-1254.
[88]
Li, Y.; Yuan, Y.Y.; Meeran, S.M.; Tollefsbol, T.O. Synergistic epigenetic reactivation of estrogen receptor-alpha (ERalpha) by combined green tea polyphenol and histone deacetylase inhibitor in ERalpha-negative breast cancer cells. Mol. Cancer, 2010, 9, 274.
[89]
Winquist, E.; Knox, J.; Ayoub, J.P.; Wood, L.; Wainman, N.; Reid, G.K.; Pearce, L.; Shah, A.; Eisenhauer, E. 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), 159-167.
[90]
Amato, R.J.; Stephenson, J.; Hotte, S.; Nemunaitis, J.; Belanger, K.; Reid, G.; Martell, R.E. MG98, a second-generation DNMT1 inhibitor, in the treatment of advanced renal cell carcinoma. Cancer Invest., 2012, 30(5), 415-421.
[91]
Plummer, R.; Vidal, L.; Griffin, M.; Lesley, M.; de Bono, J.; Coulthard, S.; Sludden, J.; Siu, L.L.; Chen, E.X.; Oza, A.M.; Reid, G.K.; McLeod, A.R.; Besterman, J.M.; Lee, C.; Judson, I.; Calvert, H.; Boddy, A.V. 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), 3177-3183.
[92]
de la Cruz-Hernandez, E. DNA demethylating activity of hydralazine in cancer cell lines. Life Sci. Med. Res., 2011.
[93]
Segura-Pacheco, B.; Trejo-Becerril, C.; Perez-Cardenas, E.; Taja-Chayeb, L.; Mariscal, I.; Chavez, A.; Acuna, C.; Salazar, A.M.; Lizano, M.; Duenas-Gonzalez, A. Reactivation of tumor suppressor genes by the cardiovascular drugs hydralazine and procainamide and their potential use in cancer therapy. Clin. Cancer Res., 2003, 9(5), 1596-1603.
[94]
Safar, A.M.; Macleod, S.; Fan, C-Y.; Hutchins, L.; Makhoul, I. Hydralazine as a demethylating agent in operable breast cancer. Cancer Res., 2006, 66(8)(Suppl.), 380-380.
[95]
Wagner, J.M.; Hackanson, B.; Lubbert, M.; Jung, M. Histone deacetylase (HDAC) inhibitors in recent clinical trials for cancer therapy. Clin. Epigenetics, 2010, 1(3-4), 117-136.
[96]
Namdar, M.; Perez, G.; Ngo, L.; Marks, P.A. Selective inhibition of histone deacetylase 6 (HDAC6) induces DNA damage and sensitizes transformed cells to anticancer agents. Proc. Natl. Acad. Sci. USA, 2010, 107(46), 20003-20008.
[97]
Candido, E.P.; Reeves, R.; Davie, J.R. Sodium butyrate inhibits histone deacetylation in cultured cells. Cell, 1978, 14(1), 105-113.
[98]
Louis, M.; Rosato, R.R.; Brault, L.; Osbild, S.; Battaglia, E.; Yang, X.H.; Grant, S.; Bagrel, D. The histone deacetylase inhibitor sodium butyrate induces breast cancer cell apoptosis through diverse cytotoxic actions including glutathione depletion and oxidative stress. Int. J. Oncol., 2004, 25(6), 1701-1711.
[99]
Cho, H.J.; Kim, S.Y.; Kim, K.H.; Kang, W.K.; Kim, J.I.; Oh, S.T.; Kim, J.S.; An, C.H. The combination effect of sodium butyrate and 5-Aza-2′-deoxycytidine on radiosensitivity in RKO colorectal cancer and MCF-7 breast cancer cell lines. World J. Surg. Oncol., 2009, 7, 49.
[100]
Travaglini, L.; Vian, L.; Billi, M.; Grignani, F.; Nervi, C. Epigenetic reprogramming of breast cancer cells by valproic acid occurs regardless of estrogen receptor status. Int. J. Biochem. Cell Biol., 2009, 41(1), 225-234.
[101]
Gottlicher, M.; Minucci, S.; Zhu, P.; Kramer, O.H.; Schimpf, A.; Giavara, S.; Sleeman, J.P.; Lo Coco, F.; Nervi, C.; Pelicci, P.G.; Heinzel, T. Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells. EMBO J., 2001, 20(24), 6969-6978.
[102]
Wawruszak, A.; Luszczki, J.J.; Grabarska, A.; Gumbarewicz, E.; Dmoszynska-Graniczka, M.; Polberg, K.; Stepulak, A. Assessment of interactions between cisplatin and two histone deacetylase inhibitors in MCF7, T47D and MDA-MB-231 human breast cancer cell lines - an isobolographic analysis. PLoS One, 2015, 10(11), e0143013.
[103]
Terranova-Barberio, M.; Roca, M.S.; Zotti, A.I.; Leone, A.; Bruzzese, F.; Vitagliano, C.; Scogliamiglio, G.; Russo, D.; D’Angelo, G.; Franco, R.; Budillon, A.; Di Gennaro, E. Valproic acid potentiates the anticancer activity of capecitabine in vitro and in vivo in breast cancer models via induction of thymidine phosphorylase expression. Oncotarget, 2016, 7(7), 7715-7731.
[104]
Atmaca, A.; Al-Batran, S.E.; Maurer, A.; Neumann, A.; Heinzel, T.; Hentsch, B.; Schwarz, S.E.; Hovelmann, S.; Gottlicher, M.; Knuth, A.; Jager, E. Valproic acid (VPA) in patients with refractory advanced cancer: a dose escalating phase I clinical trial. Br. J. Cancer, 2007, 97(2), 177-182.
[105]
Munster, P.; Marchion, D.; Bicaku, E.; Lacevic, M.; Kim, J.; Centeno, B.; Daud, A.; Neuger, A.; Minton, S.; Sullivan, D. Clinical and biological effects of valproic acid as a histone deacetylase inhibitor on tumor and surrogate tissues: phase I/II trial of valproic acid and epirubicin/FEC. Clin. Cancer Res., 2009, 15(7), 2488-2496.
[106]
Pal, D.; Saha, S. Hydroxamic acid - A novel molecule for anticancer therapy. J. Adv. Pharm. Technol. Res., 2012, 3(2), 92-99.
[107]
Reid, G.; Metivier, R.; Lin, C.Y.; Denger, S.; Ibberson, D.; Ivacevic, T.; Brand, H.; Benes, V.; Liu, E.T.; Gannon, F. Multiple mechanisms induce transcriptional silencing of a subset of genes, including oestrogen receptor alpha, in response to deacetylase inhibition by valproic acid and trichostatin A. Oncogene, 2005, 24(31), 4894-4907.
[108]
Rhodes, L.V.; Nitschke, A.M.; Segar, H.C.; Martin, E.C.; Driver, J.L.; Elliott, S.; Nam, S.Y.; Li, M.; Nephew, K.P.; Burow, M.E.; Collins-Burow, B.M. The histone deacetylase inhibitor trichostatin A alters microRNA expression profiles in apoptosis-resistant breast cancer cells. Oncol. Rep., 2012, 27(1), 10-16.
[109]
Wang, S.; Liu, Q.; Zhang, Y.; Liu, K.; Yu, P.; Luan, J.; Duan, H.; Lu, Z.; Wang, F.; Wu, E.; Yagasaki, K.; Zhang, G. Suppression of growth, migration and invasion of highly-metastatic human breast cancer cells by berbamine and its molecular mechanisms of action. Mol. Cancer, 2009, 8, 81.
[110]
Gong, C.; Qu, S.; Lv, X.B.; Liu, B.; Tan, W.; Nie, Y.; Su, F.; Liu, Q.; Yao, H.; Song, E. BRMS1L suppresses breast cancer metastasis by inducing epigenetic silence of FZD10. Nat. Commun., 2014, 5, 5406.
[111]
Bali, P.; Pranpat, M.; Swaby, R.; Fiskus, W.; Yamaguchi, H.; Balasis, M.; Rocha, K.; Wang, H.G.; Richon, V.; Bhalla, K. Activity of suberoylanilide hydroxamic Acid against human breast cancer cells with amplification of her-2. Clin. Cancer Res., 2005, 11(17), 6382-6389.
[112]
Luu, T.H.; Morgan, R.J.; Leong, L.; Lim, D.; McNamara, M.; Portnow, J.; Frankel, P.; Smith, D.D.; Doroshow, J.H.; Wong, C.; Aparicio, A.; Gandara, D.R.; Somlo, G. A phase II trial of vorinostat (suberoylanilide hydroxamic acid) in metastatic breast cancer: a California Cancer Consortium study. Clin. Cancer Res., 2008, 14(21), 7138-7142.
[113]
Stearns, V.; Jacobs, L.K.; Fackler, M.; Tsangaris, T.N.; Rudek, M.A.; Higgins, M.; Lange, J.; Cheng, Z.; Slater, S.A.; Jeter, S.C.; Powers, P.; Briest, S.; Chao, C.; Yoshizawa, C.; Sugar, E.; Espinoza-Delgado, I.; Sukumar, S.; Gabrielson, E.; Davidson, N.E. Biomarker modulation following short-term vorinostat in women with newly diagnosed primary breast cancer. Clin. Cancer Res., 2013, 19(14), 4008-4016.
[114]
Munster, P.N.; Marchion, D.; Thomas, S.; Egorin, M.; Minton, S.; Springett, G.; Lee, J.H.; Simon, G.; Chiappori, A.; Sullivan, D.; Daud, A. Phase I trial of vorinostat and doxorubicin in solid tumours: histone deacetylase 2 expression as a predictive marker. Br. J. Cancer, 2009, 101(7), 1044-1050.
[115]
Munster, P.N.; Thurn, K.T.; Thomas, S.; Raha, P.; Lacevic, M.; Miller, A.; Melisko, M.; Ismail-Khan, R.; Rugo, H.; Moasser, M.; Minton, S.E. A phase II study of the histone deacetylase inhibitor vorinostat combined with tamoxifen for the treatment of patients with hormone therapy-resistant breast cancer. Br. J. Cancer, 2011, 104(12), 1828-1835.
[116]
Ramaswamy, B.; Fiskus, W.; Cohen, B.; Pellegrino, C.; Hershman, D.L.; Chuang, E.; Luu, T.; Somlo, G.; Goetz, M.; Swaby, R.; Shapiro, C.L.; Stearns, V.; Christos, P.; Espinoza-Delgado, I.; Bhalla, K.; Sparano, J.A. Phase I-II study of vorinostat plus paclitaxel and bevacizumab in metastatic breast cancer: evidence for vorinostat-induced tubulin acetylation and Hsp90 inhibition in vivo. Breast Cancer Res. Treat., 2012, 132(3), 1063-1072.
[117]
Tate, C.R.; Rhodes, L.V.; Segar, H.C.; Driver, J.L.; Pounder, F.N.; Burow, M.E.; Collins-Burow, B.M. Targeting triple-negative breast cancer cells with the histone deacetylase inhibitor panobinostat. Breast Cancer Res., 2012, 14(3), R79.
[118]
Fortunati, N.; Marano, F.; Bandino, A.; Frairia, R.; Catalano, M.G.; Boccuzzi, G. The pan-histone deacetylase inhibitor LBH589 (panobinostat) alters the invasive breast cancer cell phenotype. Int. J. Oncol., 2014, 44(3), 700-708.
[119]
Campone, M.; Conte, P.; Amadori, D.; Pronzato, P.; Wardley, A.; McBride, K.; Fandi, A. Phase I trial of panobinostat (LBH589) in combination with trastuzumab in pretreated HER2-positive metastatic breast cancer (mBC): preliminary safety, efficacy and pharmacokinetic results. Cancer Res., 2009, 69(24)(Suppl.), 6101-6101.
[120]
Tan, W.W.; Allred, J.B.; Moreno-Aspitia, A.; Northfelt, D.W.; Ingle, J.N.; Goetz, M.P.; Perez, E.A. Phase I study of panobinostat (LBH589) and letrozole in postmenopausal metastatic breast cancer patients. Clin. Breast Cancer, 2016, 16(2), 82-86.
[121]
Chakraborty, S.; Tai, D.F.; Lin, Y.C.; Chiou, T.W. Antitumor and antimicrobial activity of some cyclic tetrapeptides and tripeptides derived from marine bacteria. Mar. Drugs, 2015, 13(5), 3029-3045.
[122]
Liu, Y.; Liggitt, D.; Fong, S.; Debs, R.J. Systemic co-administration of depsipeptide selectively targets transfection enhancement to specific tissues and cell types. Gene Ther., 2006, 13(24), 1724-1730.
[123]
Robertson, F.M.; Chu, K.; Boley, K.M.; Ye, Z.; Liu, H.; Wright, M.C.; Moraes, R.; Zhang, X.; Green, T.L.; Barsky, S.H.; Heise, C.; Cristofanilli, M. The class I HDAC inhibitor Romidepsin targets inflammatory breast cancer tumor emboli and synergizes with paclitaxel to inhibit metastasis. J. Exp. Ther. Oncol., 2013, 10(3), 219-233.
[124]
Choi, D.S.; Chang, J.C. Abstract 4129: Chloroquine and romidepsin: combination therapy for treatment of breast cancer metastases. Cancer Res., 2015, 75(15)(Suppl.), 4129-4129.
[125]
Im, J.Y.; Park, H.; Kang, K.W.; Choi, W.S.; Kim, H.S. Modulation of cell cycles and apoptosis by apicidin in estrogen receptor (ER)-positive and-negative human breast cancer cells. Chem. Biol. Interact., 2008, 172(3), 235-244.
[126]
Kim, M.S.; Son, M.W.; Kim, W.B. In Park, Y.; Moon, A., Apicidin, an inhibitor of histone deacetylase, prevents H-ras-induced invasive phenotype. Cancer Lett., 2000, 157(1), 23-30.
[127]
Park, H.; Im, J.Y.; Kim, J.; Choi, W.S.; Kim, H.S. Effects of apicidin, a histone deacetylase inhibitor, on the regulation of apoptosis in H-ras-transformed breast epithelial cells. Int. J. Mol. Med., 2008, 21(3), 325-333.
[128]
Buoncervello, M.; Borghi, P.; Romagnoli, G.; Spadaro, F.; Belardelli, F.; Toschi, E.; Gabriele, L. Apicidin and docetaxel combination treatment drives CTCFL expression and HMGB1 release acting as potential antitumor immune response inducers in metastatic breast cancer cells. Neoplasia, 2012, 14(9), 855-867.
[129]
Feng, J.; Fang, H.; Wang, X.; Jia, Y.; Zhang, L.; Jiao, J.; Zhang, J.; Gu, L.; Xu, W. Discovery of N-hydroxy-4-(3-phenylpropanamido) benzamide derivative 5j, a novel histone deacetylase inhibitor, as a potential therapeutic agent for human breast cancer. Cancer Biol. Ther., 2011, 11(5), 477-489.
[130]
Saito, A.; Yamashita, T.; Mariko, Y.; Nosaka, Y.; Tsuchiya, K.; Ando, T.; Suzuki, T.; Tsuruo, T.; Nakanishi, O. 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), 4592-4597.
[131]
Wang, S.; Huang, J.; Lyu, H.; Lee, C.K.; Tan, J.; Wang, J.; Liu, B. Functional cooperation of miR-125a, miR-125b, and miR-205 in entinostat-induced downregulation of erbB2/erbB3 and apoptosis in breast cancer cells. Cell Death Dis., 2013, 4, e556.
[132]
Srivastava, R.K.; Kurzrock, R.; Shankar, S. MS-275 sensitizes TRAIL-resistant breast cancer cells, inhibits angiogenesis and metastasis, and reverses epithelial-mesenchymal transition in vivo. Mol. Cancer Ther., 2010, 9(12), 3254-3266.
[133]
Xu, J.; Zhou, J.Y.; Wei, W.Z.; Philipsen, S.; Wu, G.S. Sp1-mediated TRAIL induction in chemosensitization. Cancer Res., 2008, 68(16), 6718-6726.
[134]
Pili, R.; Salumbides, B.; Zhao, M.; Altiok, S.; Qian, D.; Zwiebel, J.; Carducci, M.A.; Rudek, M.A. Phase I study of the histone deacetylase inhibitor entinostat in combination with 13-cis retinoic acid in patients with solid tumours. Br. J. Cancer, 2012, 106(1), 77-84.
[135]
Yardley, D.A.; Ismail-Khan, R.R.; Melichar, B.; Lichinitser, M.; Munster, P.N.; Klein, P.M.; Cruickshank, S.; Miller, K.D.; Lee, M.J.; Trepel, J.B. Randomized phase II, double-blind, placebo-controlled study of exemestane with or without entinostat in postmenopausal women with locally recurrent or metastatic estrogen receptor-positive breast cancer progressing on treatment with a nonsteroidal aromatase inhibitor. J. Clin. Oncol., 2013, 31(17), 2128-2135.
[136]
Riva, L.; Blaney, S.M.; Dauser, R.; Nuchtern, J.G.; Durfee, J.; McGuffey, L.; Berg, S.L. Pharmacokinetics and cerebrospinal fluid penetration of CI-994 (N-acetyldinaline) in the nonhuman primate. Clin. Cancer Res., 2000, 6(3), 994-997.
[137]
Undevia, S.D.; Kindler, H.L.; Janisch, L.; Olson, S.C.; Schilsky, R.L.; Vogelzang, N.J.; Kimmel, K.A.; Macek, T.A.; Ratain, M.J. A phase I study of the oral combination of CI-994, a putative histone deacetylase inhibitor, and capecitabine. Ann. Oncol., 2004, 15(11), 1705-1711.
[138]
Yang, X.; Ferguson, A.T.; Nass, S.J.; Phillips, D.L.; Butash, K.A.; Wang, S.M.; Herman, J.G.; Davidson, N.E. Transcriptional activation of estrogen receptor alpha in human breast cancer cells by histone deacetylase inhibition. Cancer Res., 2000, 60(24), 6890-6894.
[139]
Sharma, D.; Saxena, N.K.; Davidson, N.E.; Vertino, P.M. Restoration of tamoxifen sensitivity in estrogen receptor-negative breast cancer cells: tamoxifen-bound reactivated ER recruits distinctive corepressor complexes. Cancer Res., 2006, 66(12), 6370-6378.
[140]
Keen, J.C.; Yan, L.; Mack, K.M.; Pettit, C.; Smith, D.; Sharma, D.; Davidson, N.E. A novel histone deacetylase inhibitor, scriptaid, enhances expression of functional estrogen receptor alpha (ER) in ER negative human breast cancer cells in combination with 5-aza 2′-deoxycytidine. Breast Cancer Res. Treat., 2003, 81(3), 177-186.
[141]
Cooper, S.J.; von Roemeling, C.A.; Kang, K.H.; Marlow, L.A.; Grebe, S.K.; Menefee, M.E.; Tun, H.W.; Colon-Otero, G.; Perez, E.A.; Copland, J.A. Re-expression of tumor suppressor, sFRP1, leads to antitumor synergy of combined HDAC and methyltransferase inhibitors in chemoresistant cancers. Mol. Cancer Ther., 2012, 11(10), 2105-2115.
[142]
Juergens, R.A.; Wrangle, J.; Vendetti, F.P.; Murphy, S.C.; Zhao, M.; Coleman, B.; Sebree, R.; Rodgers, K.; Hooker, C.M.; Franco, N.; Lee, B.; Tsai, S.; Delgado, I.E.; Rudek, M.A.; Belinsky, S.A.; Herman, J.G.; Baylin, S.B.; Brock, M.V.; Rudin, C.M. Combination epigenetic therapy has efficacy in patients with refractory advanced non-small cell lung cancer. Cancer Discov., 2011, 1(7), 598-607.
[143]
Friday, B.B.; Anderson, S.K.; Buckner, J.; Yu, C.; Giannini, C.; Geoffroy, F.; Schwerkoske, J.; Mazurczak, M.; Gross, H.; Pajon, E.; Jaeckle, K.; Galanis, E. Phase II trial of vorinostat in combination with bortezomib in recurrent glioblastoma: a north central cancer treatment group study. Neuro-oncol., 2012, 14(2), 215-221.
[144]
Braiteh, F.; Soriano, A.O.; Garcia-Manero, G.; Hong, D.; Johnson, M.M.; Silva Lde, P.; Yang, H.; Alexander, S.; Wolff, J.; Kurzrock, R. Phase I study of epigenetic modulation with 5-azacytidine and valproic acid in patients with advanced cancers. Clin. Cancer Res., 2008, 14(19), 6296-6301.
[145]
Lin, J.; Gilbert, J.; Rudek, M.A.; Zwiebel, J.A.; Gore, S.; Jiemjit, A.; Zhao, M.; Baker, S.D.; Ambinder, R.F.; Herman, J.G.; Donehower, R.C.; Carducci, M.A. 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(19), 6241-6249.
[146]
Arce, C.; Perez-Plasencia, C.; Gonzalez-Fierro, A.; de la Cruz-Hernandez, E.; Revilla-Vazquez, A.; Chavez-Blanco, A.; Trejo-Becerril, C.; Perez-Cardenas, E.; Taja-Chayeb, L.; Bargallo, E.; Villarreal, P.; Ramirez, T.; Vela, T.; Candelaria, M.; Camargo, M.F.; Robles, E.; Duenas-Gonzalez, A. A proof-of-principle study of epigenetic therapy added to neoadjuvant doxorubicin cyclophosphamide for locally advanced breast cancer. PLoS One, 2006, 1, e98.
[147]
Candelaria, M.; Gallardo-Rincon, D.; Arce, C.; Cetina, L.; Aguilar-Ponce, J.L.; Arrieta, O.; Gonzalez-Fierro, A.; Chavez-Blanco, A.; de la Cruz-Hernandez, E.; Camargo, M.F.; Trejo-Becerril, C.; Perez-Cardenas, E.; Perez-Plasencia, C.; Taja-Chayeb, L.; Wegman-Ostrosky, T.; Revilla-Vazquez, A.; Duenas-Gonzalez, A. 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.
[148]
Connolly, R.M.; Li, H.; Jankowitz, R.C.; Zhang, Z.; Rudek, M.A.; Jeter, S.C.; Slater, S.A.; Powers, P.; Wolff, A.C.; Fetting, J.H.; Brufsky, A.; Piekarz, R.; Ahuja, N.; Laird, P.W.; Shen, H.; Weisenberger, D.J.; Cope, L.; Herman, J.G.; Somlo, G.; Garcia, A.A.; Jones, P.A.; Baylin, S.B.; Davidson, N.E.; Zahnow, C.A.; Stearns, V. Combination epigenetic therapy in advanced breast cancer with 5-azacitidine and entinostat: a phase ii national cancer institute/stand up to cancer study. Clin. Cancer Res., 2016.
[149]
Parrella, P. Epigenetic signatures in breast cancer: clinical perspective. Breast Care (Basel), 2010, 5(2), 66-73.
[150]
Fackler, M.J.; McVeigh, M.; Mehrotra, J.; Blum, M.A.; Lange, J.; Lapides, A.; Garrett, E.; Argani, P.; Sukumar, S. Quantitative multiplex methylation-specific PCR assay for the detection of promoter hypermethylation in multiple genes in breast cancer. Cancer Res., 2004, 64(13), 4442-4452.
[151]
Yamamoto, N.; Nakayama, T.; Kajita, M.; Miyake, T.; Iwamoto, T.; Kim, S.J.; Sakai, A.; Ishihara, H.; Tamaki, Y.; Noguchi, S. Detection of aberrant promoter methylation of GSTP1, RASSF1A, and RARbeta2 in serum DNA of patients with breast cancer by a newly established one-step methylation-specific PCR assay. Breast Cancer Res. Treat., 2012, 132(1), 165-173.
[152]
Sharma, G.; Mirza, S.; Parshad, R.; Srivastava, A.; Gupta, S.D.; Pandya, P.; Ralhan, R. Clinical significance of Maspin promoter methylation and loss of its protein expression in invasive ductal breast carcinoma: correlation with VEGF-A and MTA1 expression. Tumour Biol., 2011, 32(1), 23-32.
[153]
Melnikov, A.A.; Scholtens, D.M.; Wiley, E.L.; Khan, S.A.; Levenson, V.V. Array-based multiplex analysis of DNA methylation in breast cancer tissues. J. Mol. Diagn., 2008, 10(1), 93-101.
[154]
Wong, S.H.M.; Fang, C.M.; Chuah, L.H.; Leong, C.O.; Ngai, S.C. E-cadherin: Its dysregulation in carcinogenesis and clinical implications. Crit. Rev. Oncol. Hematol., 2018, 121, 11-22.
[155]
Gobel, G.; Auer, D.; Gaugg, I.; Schneitter, A.; Lesche, R.; Muller-Holzner, E.; Marth, C.; Daxenbichler, G. Prognostic significance of methylated RASSF1A and PITX2 genes in blood- and bone marrow plasma of breast cancer patients. Breast Cancer Res. Treat., 2011, 130(1), 109-117.
[156]
Avraham, A.; Uhlmann, R.; Shperber, A.; Birnbaum, M.; Sandbank, J.; Sella, A.; Sukumar, S.; Evron, E. Serum DNA methylation for monitoring response to neoadjuvant chemotherapy in breast cancer patients. Int. J. Cancer, 2012, 131(7), E1166-E1172.
[157]
Fu, D.; Ren, C.; Tan, H.; Wei, J.; Zhu, Y.; He, C.; Shao, W.; Zhang, J. Sox17 promoter methylation in plasma DNA is associated with poor survival and can be used as a prognostic factor in breast cancer. Medicine, 2015, 94(11), e637.
[158]
Zhang, Z.; Yamashita, H.; Toyama, T.; Yamamoto, Y.; Kawasoe, T.; Iwase, H. Reduced expression of the breast cancer metastasis suppressor 1 mRNA is correlated with poor progress in breast cancer. Clin. Cancer Res., 2006, 12(21), 6410-6414.
[159]
Stark, A.M.; Tongers, K.; Maass, N.; Mehdorn, H.M.; Held-Feindt, J. Reduced metastasis-suppressor gene mRNA-expression in breast cancer brain metastases. J. Cancer Res. Clin. Oncol., 2005, 131(3), 191-198.
[160]
Klajic, J.; Fleischer, T.; Dejeux, E.; Edvardsen, H.; Warnberg, F.; Bukholm, I.; Lonning, P.E.; Solvang, H.; Borresen-Dale, A.L.; Tost, J.; Kristensen, V.N. Quantitative DNA methylation analyses reveal stage dependent DNA methylation and association to clinico-pathological factors in breast tumors. BMC Cancer, 2013, 13, 456.
[161]
Fang, F.; Turcan, S.; Rimner, A.; Kaufman, A.; Giri, D.; Morris, L.G.; Shen, R.; Seshan, V.; Mo, Q.; Heguy, A.; Baylin, S.B.; Ahuja, N.; Viale, A.; Massague, J.; Norton, L.; Vahdat, L.T.; Moynahan, M.E.; Chan, T.A. Breast cancer methylomes establish an epigenomic foundation for metastasis. Sci. Transl. Med., 2011, 3(75), 75ra25.
[162]
Yu, M.; Bardia, A.; Wittner, B.S.; Stott, S.L.; Smas, M.E.; Ting, D.T.; Isakoff, S.J.; Ciciliano, J.C.; Wells, M.N.; Shah, A.M.; Concannon, K.F.; Donaldson, M.C.; Sequist, L.V.; Brachtel, E.; Sgroi, D.; Baselga, J.; Ramaswamy, S.; Toner, M.; Haber, D.A.; Maheswaran, S. Circulating breast tumor cells exhibit dynamic changes in epithelial and mesenchymal composition. Science, 2013, 339(6119), 580-584.
[163]
Howell, P.M.; Liu, Z.; Khong, H.T. Demethylating agents in the treatment of cancer. Pharmaceuticals, 2010, 3(7), 2022-2044.
[164]
Gaudet, F.; Hodgson, J.G.; Eden, A.; Jackson-Grusby, L.; Dausman, J.; Gray, J.W.; Leonhardt, H.; Jaenisch, R. Induction of tumors in mice by genomic hypomethylation. Science, 2003, 300(5618), 489-492.
[165]
Kelly, T.K.; De Carvalho, D.D.; Jones, P.A. Epigenetic modifications as therapeutic targets. Nat. Biotechnol., 2010, 28(10), 1069-1078.
[166]
Chik, F.; Machnes, Z.; Szyf, M. Synergistic anti-breast cancer effect of a combined treatment with the methyl donor S-adenosyl methionine and the DNA methylation inhibitor 5-aza-2′-deoxycytidine. Carcinogenesis, 2014, 35(1), 138-144.
[167]
Fan, M.; Yan, P.S.; Hartman-Frey, C.; Chen, L.; Paik, H.; Oyer, S.L.; Salisbury, J.D.; Cheng, A.S.; Li, L.; Abbosh, P.H.; Huang, T.H.; Nephew, K.P. Diverse gene expression and DNA methylation profiles correlate with differential adaptation of breast cancer cells to the antiestrogens tamoxifen and fulvestrant. Cancer Res., 2006, 66(24), 11954-11966.
[168]
Dokmanovic, M.; Marks, P.A. Prospects: histone deacetylase inhibitors. J. Cell. Biochem., 2005, 96(2), 293-304.
[169]
Tryndyak, V.P.; Beland, F.A.; Pogribny, I.P. E-cadherin transcriptional down-regulation by epigenetic and microRNA-200 family alterations is related to mesenchymal and drug-resistant phenotypes in human breast cancer cells. Int. J. Cancer, 2010, 126(11), 2575-2583.
[170]
Fortunati, N.; Bertino, S.; Costantino, L.; De Bortoli, M.; Compagnone, A.; Bandino, A.; Catalano, M.G.; Boccuzzi, G. Valproic acid restores ER alpha and antiestrogen sensitivity to ER alpha-negative breast cancer cells. Mol. Cell. Endocrinol., 2010, 314(1), 17-22.
[171]
Sabnis, G.J.; Goloubeva, O.; Chumsri, S.; Nguyen, N.; Sukumar, S.; Brodie, A.M. Functional activation of the estrogen receptor-alpha and aromatase by the HDAC inhibitor entinostat sensitizes ER-negative tumors to letrozole. Cancer Res., 2011, 71(5), 1893-1903.
[172]
Wong, S.T. Emerging treatment combinations: integrating therapy into clinical practice. Am. J. Health Syst. Pharm., 2009, 66(23)(Suppl. 6), S9-S14.
[173]
Primeau, M.; Gagnon, J.; Momparler, R.L. Synergistic antineoplastic action of DNA methylation inhibitor 5-AZA-2′-deoxycytidine and histone deacetylase inhibitor depsipeptide on human breast carcinoma cells. Int. J. Cancer, 2003, 103(2), 177-184.
[174]
Kelly, W.K.; O’Connor, O.A.; Krug, L.M.; Chiao, J.H.; Heaney, M.; Curley, T.; MacGregore-Cortelli, B.; Tong, W.; Secrist, J.P.; Schwartz, L.; Richardson, S.; Chu, E.; Olgac, S.; Marks, P.A.; Scher, H.; Richon, V.M. Phase I study of an oral histone deacetylase inhibitor, suberoylanilide hydroxamic acid, in patients with advanced cancer. J. Clin. Oncol., 2005, 23(17), 3923-3931.
[175]
Kelly, W.K.; Richon, V.M.; O’Connor, O.; Curley, T.; MacGregor-Curtelli, B.; Tong, W.; Klang, M.; Schwartz, L.; Richardson, S.; Rosa, E.; Drobnjak, M.; Cordon-Cordo, C.; Chiao, J.H.; Rifkind, R.; Marks, P.A.; Scher, H. Phase I clinical trial of histone deacetylase inhibitor: suberoylanilide hydroxamic acid administered intravenously. Clin. Cancer Res., 2003, 9(10 Pt 1), 3578-3588.
[176]
Vansteenkiste, J.; Van Cutsem, E.; Dumez, H.; Chen, C.; Ricker, J.L.; Randolph, S.S.; Schoffski, P. Early phase II trial of oral vorinostat in relapsed or refractory breast, colorectal, or non-small cell lung cancer. Invest. New Drugs, 2008, 26(5), 483-488.
[177]
Reddy, J.P.; Dawood, S.; Mitchell, M.; Debeb, B.G.; Bloom, E.; Gonzalez-Angulo, A.M.; Sulman, E.P.; Buchholz, T.A.; Woodward, W.A. Antiepileptic drug use improves overall survival in breast cancer patients with brain metastases in the setting of whole brain radiotherapy. Radiother. Oncol., 2015, 117(2), 308-314.
[178]
Deming, D.A.; Ninan, J.; Bailey, H.H.; Kolesar, J.M.; Eickhoff, J.; Reid, J.M.; Ames, M.M.; McGovern, R.M.; Alberti, D.; Marnocha, R.; Espinoza-Delgado, I.; Wright, J.; Wilding, G.; Schelman, W.R. A Phase I study of intermittently dosed vorinostat in combination with bortezomib in patients with advanced solid tumors. Invest. New Drugs, 2014, 32(2), 323-329.
[179]
Fu, S.; Hou, M.M.; Naing, A.; Janku, F.; Hess, K.; Zinner, R.; Subbiah, V.; Hong, D.; Wheler, J.; Piha-Paul, S.; Tsimberidou, A.; Karp, D.; Araujo, D.; Kee, B.; Hwu, P.; Wolff, R.; Kurzrock, R.; Meric-Bernstam, F. Phase I study of pazopanib and vorinostat: a therapeutic approach for inhibiting mutant p53-mediated angiogenesis and facilitating mutant p53 degradation. Ann. Oncol., 2015, 26(5), 1012-1018.
[180]
Strickler, J.H.; Starodub, A.N.; Jia, J.; Meadows, K.L.; Nixon, A.B.; Dellinger, A.; Morse, M.A.; Uronis, H.E.; Marcom, P.K.; Zafar, S.Y.; Haley, S.T.; Hurwitz, H.I. Phase I study of bevacizumab, everolimus, and panobinostat (LBH-589) in advanced solid tumors. Cancer Chemother. Pharmacol., 2012, 70(2), 251-258.
[181]
Jones, S.F.; Infante, J.R.; Thompson, D.S.; Mohyuddin, A.; Bendell, J.C.; Yardley, D.A.; Burris, H.A., III A phase I trial of oral administration of panobinostat in combination with paclitaxel and carboplatin in patients with solid tumors. Cancer Chemother. Pharmacol., 2012, 70(3), 471-475.

Rights & Permissions Print Cite
Article Metrics
84
8
© 2024 Bentham Science Publishers | Privacy Policy