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Journal of Mammary Gland Biology and Neoplasia
Published in: Journal of Mammary Gland Biology and Neoplasia 3-4/2012

01-12-2012

Epigenetics as a Therapeutic Target in Breast Cancer

Authors: Roisin Connolly, Vered Stearns

Published in: Journal of Mammary Gland Biology and Neoplasia | Issue 3-4/2012

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Abstract

Epigenetics refers to alterations in gene expression due to modifications in histone acetylation and DNA methylation at the promoter regions of genes. Unlike genetic mutations, epigenetic alterations are not due to modifications in the gene primary nucleotide sequence. The importance of epigenetics in the initiation and progression of breast cancer has led many investigators to incorporate this novel and exciting field in breast cancer drug development. Several drugs that target epigenetic alterations, including inhibitors of histone deacetylase (HDAC) and DNA methyltransferase (DNMT), are currently approved for treatment of hematological malignancies and are available for clinical investigation in solid tumors. In this manuscript, we review the critical role of epigenetics in breast cancer including the potential for epigenetic alterations to serve as biomarkers determining breast cancer prognosis and response to therapy. We highlight initial promising results to date with use of epigenetic modifiers in patients with breast cancer and the ongoing challenges involved in the successful establishment of these agents for the treatment of breast cancer.
Literature
1.
Herman JG, Baylin SB. Gene silencing in cancer in association with promoter hypermethylation. N Engl J Med. 2003;349:2042–54.PubMedCrossRef
2.
Munshi A, Shafi G, Aliya N, Jyothy A. Histone modifications dictate specific biological readouts. J Genet Genomics. 2009;36:75–88.PubMedCrossRef
3.
4.
Jones PA, Baylin SB. The fundamental role of epigenetic events in cancer. Nat Rev Genet. 2002;3:415–28.PubMedCrossRef
5.
Arts J, de Schepper S, Van Emelen K. Histone deacetylase inhibitors: from chromatin remodeling to experimental cancer therapeutics. Curr Med Chem. 2003;10:2343–50.PubMedCrossRef
6.
Prince HM, Bishton MJ, Harrison SJ. Clinical studies of histone deacetylase inhibitors. Clin Cancer Res. 2009;15:3958–69.PubMedCrossRef
7.
Pedrali-Noy G, Weissbach A. Mammalian DNA methyltransferases prefer poly(dI-dC) as substrate. J Biol Chem. 1986;261:7600–2.PubMed
8.
Okano M, Bell DW, Haber DA, Li E. DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell. 1999;99:247–57.PubMedCrossRef
9.
Fackler MJ, Rivers A, Teo WW, et al. Hypermethylated genes as biomarkers of cancer in women with pathologic nipple discharge. Clin Cancer Res. 2009;15:3802–11.PubMedCrossRef
10.
Esteller M, Garcia-Foncillas J, Andion E, et al. Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents. N Engl J Med. 2000;343:1350–4.PubMedCrossRef
11.
Brock MV, Hooker CM, Ota-Machida E, et al. DNA methylation markers and early recurrence in stage I lung cancer. N Engl J Med. 2008;358:1118–28.PubMedCrossRef
12.
Ordentlich P. Pharmacodynamic analysis of ENCORE 301, a placebo-controlled, randomized phase 2 study of exemestane with and without entinostat in postmenopausal ER + breast cancer patients demonstrates an association of lysine hyperacetylation with clinical outcome. Presented at the AACR Molecular Targets Conference 2011 (Abstract PR-6).
13.
Munster PN, Marchion D, Thomas S, et al. Phase I trial of vorinostat and doxorubicin in solid tumours: histone deacetylase 2 expression as a predictive marker. Br J Cancer. 2009;101:1044–50.PubMedCrossRef
14.
Hodges-Gallagher L, Valentine CD, Bader SE, Kushner PJ. Inhibition of histone deacetylase enhances the anti-proliferative action of antiestrogens on breast cancer cells and blocks tamoxifen-induced proliferation of uterine cells. Breast Cancer Res Treat. 2007;105:297–309.PubMedCrossRef
15.
Munster PN, Thurn KT, Thomas S, et al. 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;104:1828–35.PubMedCrossRef
16.
17.
Fackler MJ, McVeigh M, Mehrotra J, et al. Quantitative multiplex methylation-specific PCR assay for the detection of promoter hypermethylation in multiple genes in breast cancer. Cancer Res. 2004;64:4442–52.PubMedCrossRef
18.
Esteller M. Cancer epigenomics: DNA methylomes and histone-modification maps. Nat Rev Genet. 2007;8:286–98.PubMedCrossRef
19.
Pomraning KR, Smith KM, Freitag M. Genome-wide high throughput analysis of DNA methylation in eukaryotes. Methods. 2009;47(3):142–50.PubMedCrossRef
20.
Gore SD, Weng LJ, Zhai S, et al. Impact of the putative differentiating agent sodium phenylbutyrate on myelodysplastic syndromes and acute myeloid leukemia. Clin Cancer Res. 2001;7:2330–9.PubMed
21.
Olsen EA, Kim YH, Kuzel TM, et al. Phase IIb multicenter trial of vorinostat in patients with persistent, progressive, or treatment refractory cutaneous T-cell lymphoma. J Clin Oncol. 2007;25:3109–15.PubMedCrossRef
22.
Piekarz RL, Frye R, Turner M, et al. Phase II multi-institutional trial of the histone deacetylase inhibitor romidepsin as monotherapy for patients with cutaneous T-cell lymphoma. J Clin Oncol. 2009;27:5410–7.PubMedCrossRef
23.
Piekarz RL, Frye R, Prince HM, et al. Phase II trial of romidepsin in patients with peripheral T-cell lymphoma. Blood. 2011;117(22):5827–34.
24.
Whittaker SJ, Demierre MF, Kim EJ, et al. Final results from a multicenter, international, pivotal study of romidepsin in refractory cutaneous T-cell lymphoma. J Clin Oncol. 2010;28:4485–91.PubMedCrossRef
25.
Jones PA, Taylor SM. Cellular differentiation, cytidine analogs and DNA methylation. Cell. 1980;20:85–93.PubMedCrossRef
26.
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;25:4727–41.PubMedCrossRef
27.
Qin T, Youssef EM, Jelinek J, et al. Effect of cytarabine and decitabine in combination in human leukemic cell lines. Clin Cancer Res. 2007;13:4225–32.PubMedCrossRef
28.
Cowan LA, Talwar S, Yang AS. Will DNA methylation inhibitors work in solid tumors? A review of the clinical experience with azacitidine and decitabine in solid tumors. Epigenomics. 2010;2:71–86.PubMedCrossRef
29.
Fenaux P, Mufti GJ, Hellstrom-Lindberg E, et al. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol. 2009;10:223–32.PubMedCrossRef
30.
Steensma DP, Baer MR, Slack JL, et al. Multicenter study of decitabine administered daily for 5 days every 4 weeks to adults with myelodysplastic syndromes: the alternative dosing for outpatient treatment (ADOPT) trial. J Clin Oncol. 2009;27:3842–8.PubMedCrossRef
31.
Miyake K, Yoshizumi T, Imura S, et al. Expression of hypoxia-inducible factor-1alpha, histone deacetylase 1, and metastasis-associated protein 1 in pancreatic carcinoma: correlation with poor prognosis with possible regulation. Pancreas. 2008;36:e1–9.PubMedCrossRef
32.
Krusche CA, Wulfing P, Kersting C, et al. Histone deacetylase-1 and -3 protein expression in human breast cancer: a tissue microarray analysis. Breast Cancer Res Treat. 2005;90:15–23.PubMedCrossRef
33.
Zhang Z, Yamashita H, Toyama T, et al. HDAC6 expression is correlated with better survival in breast cancer. Clin Cancer Res. 2004;10:6962–8.PubMedCrossRef
34.
Soares J, Pinto AE, Cunha CV, et al. Global DNA hypomethylation in breast carcinoma: correlation with prognostic factors and tumor progression. Cancer. 1999;85:112–8.PubMedCrossRef
35.
Gupta A, Godwin AK, Vanderveer L, Lu A, Liu J. Hypomethylation of the synuclein gamma gene CpG island promotes its aberrant expression in breast carcinoma and ovarian carcinoma. Cancer Res. 2003;63:664–73.PubMed
36.
37.
Pu RT, Laitala LE, Alli PM, Fackler MJ, Sukumar S, Clark DP. Methylation profiling of benign and malignant breast lesions and its application to cytopathology. Mod Pathol. 2003;16:1095–101.PubMedCrossRef
38.
Fackler MJ, McVeigh M, Evron E, et al. DNA methylation of RASSF1A, HIN-1, RAR-beta, Cyclin D2 and Twist in in situ and invasive lobular breast carcinoma. Int J Cancer. 2003;107:970–5.PubMedCrossRef
39.
Sebova K, Zmetakova I, Bella V, et al. RASSF1A and CDH1 hypermethylation as potential epimarkers in breast cancer. Cancer Biomark. 2011;10:13–26.PubMed
40.
Tserga A, Michalopoulos NV, Levidou G, et al. Association of aberrant DNA methylation with clinicopathological features. Oncol Rep. 2012;27(5):1630–8.
41.
Lapidus RG, Nass SJ, Butash KA, et al. Mapping of ER gene CpG island methylation-specific polymerase chain reaction. Cancer research. 1998;58:2515–9.PubMed
42.
Fackler MJ, Umbricht CB, Williams D, et al. Genome-wide methylation analysis identifies genes specific to breast cancer hormone receptor status and risk of recurrence. Cancer Res. 2011;71:6195–207.PubMedCrossRef
43.
Hill VK, Ricketts C, Bieche I, et al. Genome-wide DNA methylation profiling of CpG islands in breast cancer identifies novel genes associated with tumorigenicity. Cancer Res. 2011;71:2988–99.PubMedCrossRef
44.
Perou CM, Sorlie T, Eisen MB, et al. Molecular portraits of human breast tumours. Nature. 2000;406:747–52.PubMedCrossRef
45.
Dedeurwaerder S, Desmedt C, Calonne E, et al. DNA methylation profiling reveals a predominant immune component in breast cancers. EMBO Mol Med. 2011;3:726–41.PubMedCrossRef
46.
Fong PC, Boss DS, Yap TA, et al. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med. 2009;361:123–34.PubMedCrossRef
47.
Veeck J, Ropero S, Setien F, et al. BRCA1 CpG island hypermethylation predicts sensitivity to poly(adenosine diphosphate)-ribose polymerase inhibitors. J Clin Oncol. 2010;28:e563–4. author reply e5-6.PubMedCrossRef
48.
Schrauder MG, Strick R, Schulz-Wendtland R, et al. Circulating Micro-RNAs as potential blood-based markers for early stage breast cancer detection. PLoS One. 2011;7:e29770.CrossRef
49.
Ferracin M, Querzoli P, Calin GA, Negrini M. MicroRNAs: toward the clinic for breast cancer patients. Semin Oncol. 2011;38:764–75.PubMedCrossRef
50.
Lujambio A, Esteller M. CpG island hypermethylation of tumor suppressor microRNAs in human cancer. Cell Cycle. 2007;6:1455–9.PubMedCrossRef
51.
Said TK, Moraes RC, Sinha R, Medina D. Mechanisms of suberoylanilide hydroxamic acid inhibition of mammary cell growth. Breast Cancer Res. 2001;3:122–33.PubMedCrossRef
52.
Munster PN, Troso-Sandoval T, Rosen N, Rifkind R, Marks PA, Richon VM. The histone deacetylase inhibitor suberoylanilide hydroxamic acid induces differentiation of human breast cancer cells. Cancer Res. 2001;61:8492–7.PubMed
53.
Cohen LA, Amin S, Marks PA, Rifkind RA, Desai D, Richon VM. Chemoprevention of carcinogen-induced mammary tumorigenesis by the hybrid polar cytodifferentiation agent, suberanilohydroxamic acid (SAHA). Anticancer Res. 1999;19:4999–5005.PubMed
54.
Huang L, Pardee AB. Suberoylanilide hydroxamic acid as a potential therapeutic agent for human breast cancer treatment. Mol Med. 2000;6:849–66.PubMed
55.
Keen JC, Yan L, Mack KM, et al. 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;81:177–86.PubMedCrossRef
56.
Zhou Q, Shaw PG, Davidson NE. Inhibition of histone deacetylase suppresses EGF signaling pathways by destabilizing EGFR mRNA in ER-negative human breast cancer cells. Breast Cancer Res Treat. 2009;117(2):443–51.PubMedCrossRef
57.
Sharma D, Saxena NK, Davidson NE, Vertino PM. Restoration of tamoxifen sensitivity in estrogen receptor-negative breast cancer cells: tamoxifen-bound reactivated ER recruits distinctive corepressor complexes. Cancer Res. 2006;66:6370–8.PubMedCrossRef
58.
Sabnis GJ, Goloubeva O, Chumsri S, Nguyen N, Sukumar S, Brodie AM. Functional activation of the estrogen receptor-alpha and aromatase by the HDAC inhibitor entinostat sensitizes ER-negative tumors to letrozole. Cancer Res. 2011;71:1893–903.PubMedCrossRef
59.
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;61:7025–9.PubMed
60.
Fan J, Yin WJ, Lu JS, et al. ER alpha negative breast cancer cells restore response to endocrine therapy by combination treatment with both HDAC inhibitor and DNMT inhibitor. J Cancer Res Clin Oncol. 2008;134:883–90.PubMedCrossRef
61.
Cassidy J, Lippman M, Lacroix A, Peck G. Phase II trial of 13-cis-retinoic acid in metastatic breast cancer. Eur J Cancer Clin Oncol. 1982;18:925–8.PubMedCrossRef
62.
Veronesi U, Mariani L, Decensi A, et al. Fifteen-year results of a randomized phase III trial of fenretinide to prevent second breast cancer. Ann Oncol. 2006;17:1065–71.PubMedCrossRef
63.
Kim MS, Blake M, Baek JH, Kohlhagen G, Pommier Y, Carrier F. Inhibition of histone deacetylase increases cytotoxicity to anticancer drugs targeting DNA. Cancer Res. 2003;63:7291–300.PubMed
64.
Fuino L, Bali P, Wittmann S, et al. Histone deacetylase inhibitor LAQ824 down-regulates Her-2 and sensitizes human breast cancer cells to trastuzumab, taxotere, gemcitabine, and epothilone B. Mol Cancer Ther. 2003;2:971–84.PubMed
65.
Huang X, Wang S, Lee CK, Yang X, Liu B. HDAC inhibitor SNDX-275 enhances efficacy of trastuzumab in erbB2-overexpressing breast cancer cells and exhibits potential to overcome trastuzumab resistance. Cancer Lett. 2011;307:72–9.PubMedCrossRef
66.
Bali P, Pranpat M, Swaby R, et al. Activity of suberoylanilide hydroxamic Acid against human breast cancer cells with amplification of her-2. Clin Cancer Res. 2005;11:6382–9.PubMedCrossRef
67.
Tsai HC, Li H, Van Neste L, et al. Transient Low Doses of DNA Demethylating Agents Exert Durable Anti-tumor Effects on Hematological and Epithelial Tumor Cells. Cancer Cell. 2012;21(3):430–46.
68.
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;25:1029–32.PubMedCrossRef
69.
Krawczyk B, Rudnicka K, Fabianowska-Majewska K. The effects of nucleoside analogues on promoter methylation of selected tumor suppressor genes in MCF-7 and MDA-MB-231 breast cancer cell lines. Nucleosides Nucleotides Nucleic Acids. 2007;26:1043–6.PubMedCrossRef
70.
Wozniak RJ, Klimecki WT, Lau SS, Feinstein Y, Futscher BW. 5-Aza-2′-deoxycytidine-mediated reductions in G9A histone methyltransferase and histone H3 K9 di-methylation levels are linked to tumor suppressor gene reactivation. Oncogene. 2007;26:77–90.PubMedCrossRef
71.
Xu J, Zhou JY, Tainsky MA, Wu GS. 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;67:1203–11.PubMedCrossRef
72.
Kelly WK, O’Connor OA, Krug LM, et al. Phase I study of an oral histone deacetylase inhibitor, suberoylanilide hydroxamic acid, in patients with advanced cancer. J Clin Oncol. 2005;23:3923–31.PubMedCrossRef
73.
Luu TH, Morgan RJ, Leong L, et al. A phase II trial of vorinostat (suberoylanilide hydroxamic acid) in metastatic breast cancer: a California Cancer Consortium study. Clin Cancer Res. 2008;14:7138–42.PubMedCrossRef
74.
Stearns V, Jacobs LK, Tsangaris TN, et al. Association of vorinostat with decrease in gene expression of proliferation-related genes in tumors from women with newly diagnosed breast cancer. Abs 3097. Journal of Clinical Oncology (suppl). 2010;28.
75.
Yardley DA, Ismail-Khan RR, Klein PM. Entinostat, a Novel histone deacetylase inhibitor, added to exemestane improves PFS in advanced breast cancer in a randomized, phase II, Double-blind study. Presented at the San Antonio Breast Cancer Symposium 2011 (Abstract PD01-04).
76.
77.
Ramalingam SS, Parise RA, Ramanathan RK, et al. Phase I and pharmacokinetic study of vorinostat, a histone deacetylase inhibitor, in combination with carboplatin and paclitaxel for advanced solid malignancies. Clin Cancer Res. 2007;13:3605–10.PubMedCrossRef
78.
Ramaswamy B, Fiskus W, Cohen B, et al. 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):1063–72.
79.
Gray R, Bhattacharya S, Bowden C, Miller K, Comis RL. Independent review of E2100: a phase III trial of bevacizumab plus paclitaxel versus paclitaxel in women with metastatic breast cancer. J Clin Oncol. 2009;27:4966–72.PubMedCrossRef
80.
Connolly RM, Leal JP, et al. Early change in 18-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) predicts response to preoperative systemic therapy (PST) in HER2-negative primary operable breast cancer: translational breast cancer research consortium (TBCRC008). Presented at the American Society of Clinical Oncology (ASCO) meeting 2012. J Clin Oncol. 2012;30(suppl; abstr 10509).
81.
Raffoux E, Cras A, Recher C, et al. Phase 2 clinical trial of 5-azacitidine, valproic acid, and all-trans retinoic acid in patients with high-risk acute myeloid leukemia or myelodysplastic syndrome. Oncotarget. 2010;1:34–42.PubMed
82.
83.
84.
Gore SD, Baylin S, Sugar E, et al. Combined DNA methyltransferase and histone deacetylase inhibition in the treatment of myeloid neoplasms. Cancer Res. 2006;66:6361–9.PubMedCrossRef
85.
Juergens RA, Wrangle J, Vendetti FP, et al. Combination epigenetic therapy has efficacy in patients with refractory advanced non–small cell lung cancer. Cancer Discovery. 2011;1(7):598–607.
86.
Weiss AJ, Metter GE, Nealon TF, et al. Phase II study of 5-azacytidine in solid tumors. Cancer Treat Rep. 1977;61:55–8.PubMed
87.
Weiss AJ, Stambaugh JE, Mastrangelo MJ, Laucius JF, Bellet RE. Phase I study of 5-azacytidine (NSC-102816). Cancer Chemother Rep. 1972;56:413–9.PubMed
88.
89.
Connolly RM, Jankowitz RC, Andreopoulou E, et al. A Phase 2 study investigating the safety, efficacy and surrogate biomarkers of response of 5-Azacitidine (5-AZA) and Entinostat (MS-275) in Patients with Advanced Breast Cancer. SABCS 2011 Ongoing Trials Session (Abs OT3 − 01 − 06).
90.
Stathis A, Hotte SJ, Chen EX, et al. Phase I study of decitabine in combination with vorinostat in patients with advanced solid tumors and non-Hodgkin’s lymphomas. Clin Cancer Res. 2011;17:1582–90.PubMedCrossRef
91.
Fu S, Hu W, Iyer R, et al. Phase 1b-2a study to reverse platinum resistance through use of a hypomethylating agent, azacitidine, in patients with platinum-resistant or platinum-refractory epithelial ovarian cancer. Cancer. 2011;117:1661–9.PubMedCrossRef
92.
93.
Scandura JM, Roboz GJ, Moh M, et al. Phase 1 study of epigenetic priming with decitabine prior to standard induction chemotherapy for patients with AML. Blood. 2011;118:1472–80.PubMedCrossRef
94.
Chuang JC, Warner SL, Vollmer D, 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.PubMedCrossRef
95.
Foulks JM, Parnell KM, Nix RN, et al. Epigenetic drug discovery: targeting DNA methyltransferases. J Biomol Screen. 2011;17:2–17.PubMedCrossRef
96.
Yao Y, Chen P, Diao J, et al. Selective inhibitors of histone methyltransferase DOT1L: design, synthesis, and crystallographic studies. J Am Chem Soc. 2011;133:16746–9.PubMedCrossRef
97.
Huang Y, Vasilatos SN, Boric L, Shaw PG, Davidson NE. Inhibitors of histone demethylation and histone deacetylation cooperate in regulating gene expression and inhibiting growth in human breast cancer cells. Breast Cancer Res Treat. 2012;131(3):777–89.
98.
Metzeler KH, Walker A, Geyer S, et al. DNMT3A mutations and response to the hypomethylating agent decitabine in acute myeloid leukemia. Leukemia. 2012;26(5):1106–7.
99.
Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47.PubMedCrossRef
100.
Wolchok JD, Hoos A, O’Day S, et al. Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res. 2009;15:7412–20.PubMedCrossRef
Metadata
Title
Epigenetics as a Therapeutic Target in Breast Cancer
Authors
Roisin Connolly
Vered Stearns
Publication date
01-12-2012
Publisher
Springer US
Published in
Journal of Mammary Gland Biology and Neoplasia / Issue 3-4/2012
Print ISSN: 1083-3021
Electronic ISSN: 1573-7039
DOI
https://doi.org/10.1007/s10911-012-9263-3

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