Rational therapeutic combinations with histone deacetylase inhibitors for the treatment of cancer

Future Oncology

Volumn 7, Issue 2, 2011, Pages 263-283

  Thurn, K Ted ^a   Thomas, Scott ^a   Moore, Amy ^a   Munster, Pamela N ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

clinical trial; combination therapy; HDAC inhibitor; histone deacetylase

Indexed keywords

BELINOSTAT; BEVACIZUMAB; CAPECITABINE; CARBOPLATIN; CYCLOPHOSPHAMIDE; DNA METHYLTRANSFERASE INHIBITOR; DOXORUBICIN; ENTINOSTAT; ERLOTINIB; ETOPOSIDE; EVEROLIMUS; FLUOROURACIL; FOLINIC ACID; GEFITINIB; GEMCITABINE; HISTONE DEACETYLASE INHIBITOR; ISOTRETINOIN; LAPATINIB; PACLITAXEL; PANOBINOSTAT; PCI 24781; RITUXIMAB; ROMIDEPSIN; SORAFENIB; TEMOZOLOMIDE; TRASTUZUMAB; UNCLASSIFIED DRUG; UNINDEXED DRUG; VALPROIC ACID; VINCRISTINE; VORINOSTAT;

ACETYLATION; ACUTE GRANULOCYTIC LEUKEMIA; BREAST CANCER; CANCER COMBINATION CHEMOTHERAPY; CANCER RADIOTHERAPY; CLINICAL TRIAL; COLORECTAL CANCER; CUTANEOUS T CELL LYMPHOMA; DIARRHEA; DNA DAMAGE; DNA REPAIR; FATIGUE; GENETIC TRANSCRIPTION; GLIOBLASTOMA; GLIOMA; HORMONAL THERAPY; HUMAN; KIDNEY CANCER; KIDNEY CARCINOMA; LARGE CELL LYMPHOMA; LUNG NON SMALL CELL CANCER; LYMPHOMA; MESOTHELIOMA; MULTIMODALITY CANCER THERAPY; MULTIPLE CYCLE TREATMENT; MYCOSIS FUNGOIDES; MYELODYSPLASTIC SYNDROME; NAUSEA; NEUTROPENIA; OVARY CANCER; PANCREAS CANCER; PERITONEUM CANCER; PRIORITY JOURNAL; PROSTATE CANCER; PRURITUS; REVIEW; SARCOMA; SEZARY SYNDROME; SMALL CELL CARCINOMA; SOFT TISSUE CANCER; SOFT TISSUE SARCOMA; T CELL LYMPHOMA; THROMBOCYTOPENIA; THYMUS CANCER; UTERINE CERVIX CANCER; UTERINE TUBE CARCINOMA; VOMITING;

ACETYLATION; ANTINEOPLASTIC AGENTS; CHROMATIN; DNA REPAIR; GENE EXPRESSION REGULATION, NEOPLASTIC; HISTONE DEACETYLASE INHIBITORS; HISTONE DEACETYLASES; HUMANS; MICROTUBULES; MOLECULAR TARGETED THERAPY; NEOPLASMS;

EID: 79952158522     PISSN: 14796694     EISSN: 17448301     Source Type: Journal    
DOI: 10.2217/fon.11.2     Document Type: Review

References (177)

1. Marks PA, Richon VM, Miller T, Kelly WK: Histone deacetylase inhibitors. Adv. Cancer Res. 91, 137-168 (2004).
2. Yang WM, Tsai SC, Wen YD, Fejer G, Seto E: Functional domains of histone deacetylase-3. J. Biol. Chem. 277(11), 9447-9454 (2002).
3. Yang WM, Yao YL, Sun JM, Davie JR, Seto E: Isolation and characterization of cDNAs corresponding to an additional member of the human histone deacetylase gene family. J. Biol. Chem. 272(44), 28001-28007 (1997).
4. Cen Y: Sirtuins inhibitors: the approach to affinity and selectivity. Biochim. Biophys. Acta 1804(8), 1635-1644 (2010).
5. Vigushin DM, Coombes RC: Histone deacetylase inhibitors in cancer treatment. Anticancer Drugs 13(1), 1-13 (2002).
6. Marks P, Rifkind RA, Richon VM, Breslow R, Miller T, Kelly WK: Histone deacetylases and cancer: causes and therapies. Nat. Rev. Cancer 1(3), 194-202 (2001).
7. Jung M: Inhibitors of histone deacetylase as new anticancer agents. Curr. Med. Chem. 8(12), 1505-1511 (2001).
8. Kelly WK, O'Connor OA, Marks PA: Histone deacetylase inhibitors: from target to clinical trials. Expert Opin. Investig. Drugs 11(12), 1695-1713 (2002).
9. Arts J, De Schepper S, Van Emelen K: Histone deacetylase inhibitors: from chromatin remodeling to experimental cancer therapeutics. Curr. Med. Chem. 10(22), 2343-2350 (2003).
10. Sengupta N, Seto E: Regulation of histone deacetylase activities. J. Cell. Biochem. 93(1), 57-67 (2004).
11. Dokmanovic M, Marks PA: Prospects: histone deacetylase inhibitors. J. Cell. Biochem. 96(2), 293-304 (2005).
12. Bradner JE, West N, Grachan ML et al.: Chemical phylogenetics of histone deacetylases. Nat. Chem. Biol. 6(3), 238-243 (2010).
13. Khan O, La Thangue NB: Drug insight: histone deacetylase inhibitor-based therapies for cutaneous T-cell lymphomas. Nat. Clin. Pract. Oncol. 5(12), 714-726 (2008).
14. Stimson L, Wood V, Khan O, Fotheringham S, La Thangue NB: HDAC inhibitor-based therapies and haematological malignancy. Ann. Oncol. 20(8), 1293-1302 (2009).
15. 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. 25(21), 3109-3115 (2007). Phase IIb clinical trial in patients with cutaneous T-cell lymphoma demonstrating a nearly 30% objective response when treated with vorinostat monotherapy.
16. Duvic M, Talpur R, Ni X et al.: Phase II trial of oral vorinostat (suberoylanilide hydroxamic acid, SAHA) for refractory cutaneous T-cell lymphoma (CTCL). Blood 109(1), 31-39 (2007).
17. Blum W, Marcucci G: Targeting epigenetic changes in acute myeloid leukemia. Clin. Adv. Hematol. Oncol. 3(11), 855-865, 882 (2005).
18. Garcia-Manero G, Yang H, Bueso-Ramos C et al.: Phase 1 study of the histone deacetylase inhibitor vorinostat (suberoylanilide hydroxamic acid [SAHA]) in patients with advanced leukemias and myelodysplastic syndromes. Blood 111(3), 1060-1066 (2008).
19. Siegel D, Hussein M, Belani C et al.: Vorinostat in solid and hematologic malignancies. J. Hematol. Oncol. 2, 31 (2009).
20. 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. 27(32), 5410-5417 (2009). Romidepsin treatment for patients with cutaneous T-cell lymphoma resulted in a 34% overall response rate, including four complete responses and 20 partial responses out of 71 patients.
21. 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. 28(29), 4485-4491 (2010).
22. Munster P, Marchion D, Bicaku E et al.: Phase I trial of histone deacetylase inhibition by valproic acid followed by the topoisomerase II inhibitor epirubicin in advanced solid tumors: a clinical and translational study. J. Clin. Oncol. 25(15), 1979-1985 (2007). Phase I trial investigating the effect of adding epirubicin after valproic acid treatment in patients with advanced solid tumors. Of the 41 patients, there were nine partial responses (22%) and 16 stable diseases (39%).
23. Yang XJ, Seto E: HATs and HDACs: from structure, function and regulation to novel strategies for therapy and prevention. Oncogene 26(37), 5310-5318 (2007).
24. Daud A, Schmitt M, Marchion D et al.: Phase I trial of a sequence-specific combination of the HDAC inhibitor, vorinostat followed by doxorubicin in solid tumor malignancies. J. Clin. Oncol. 25(Suppl. 18), 3502 (2007).
25. 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 101(7), 1044-1050 (2009).
26. Marchion DC, Bicaku E, Daud AI, Sullivan DM, Munster PN: Valproic acid alters chromatin structure by regulation of chromatin modulation proteins. Cancer Res. 65(9), 3815-3822 (2005).
27. Marchion DC, Bicaku E, Turner JG, Schmitt ML, Morelli DR, Munster PN: HDAC2 regulates chromatin plasticity and enhances DNA vulnerability. Mol. Cancer Ther. 8(4), 794-801 (2009).
28. Ma YL, Bryant HU, Zeng Q et al.: Long-term dosing of arzoxifene lowers cholesterol, reduces bone turnover, and preserves bone quality in ovariectomized rats. J. Bone Miner. Res. 17(12), 2256-2264 (2002).
29. Marchion DC, Bicaku E, Daud AI, Richon V, Sullivan DM, Munster PN: Sequence-specific potentiation of topoisomerase II inhibitors by the histone deacetylase inhibitor suberoylanilide hydroxamic acid. J. Cell. Biochem. 92(2), 223-237 (2004).
30. Marchion DC, Bicaku E, Daud AI, Sullivan DM, Munster PN: In vivo synergy between topoisomerase II and histone deacetylase inhibitors: predictive correlates. Mol. Cancer Ther. 4(12), 1993-2000 (2005).
31. Baschnagel A, Russo A, Burgan WE et al.: Vorinostat enhances the radiosensitivity of a breast cancer brain metastatic cell line grown in vitro and as intracranial xenografts. Mol. Cancer Ther. 8(6), 1589-1595 (2009).
32. Geng L, Cuneo KC, Fu A, Tu T, Atadja PW, Hallahan DE: Histone deacetylase (HDAC) inhibitor LBH589 increases duration of γ-H2AX foci and confines HDAC4 to the cytoplasm in irradiated non-small cell lung cancer. Cancer Res. 66(23), 11298-11304 (2006).
33. Munshi A, Kurland JF, Nishikawa T et al.: Histone deacetylase inhibitors radiosensitize human melanoma cells by suppressing DNA repair activity. Clin. Cancer Res. 11(13), 4912-4922 (2005).
34. Gatei M, Scott SP, Filippovitch I et al.: Role for ATM in DNA damage-induced phosphorylation of BRCA1. Cancer Res. 60(12), 3299-3304 (2000).
35. Chen CS, Wang YC, Yang HC et al.: Histone deacetylase inhibitors sensitize prostate cancer cells to agents that produce DNA double-strand breaks by targeting Ku70 acetylation. Cancer Res. 67(11), 5318-5327 (2007).
36. Kachhap SK, Rosmus N, Collis SJ et al.: Downregulation of homologous recombination DNA repair genes by HDAC inhibition in prostate cancer is mediated through the E2F1 transcription factor. PLoS One 5(6), E11208 (2010).
37. Zhang Y, Carr T, Dimtchev A, Zaer N, Dritschilo A, Jung M: Attenuated DNA damage repair by trichostatin a through BRCA1 suppression. Radiat. Res. 168(1), 115-124 (2007).
38. Burkitt K, Ljungman M: Phenylbutyrate interferes with the fanconi anemia and BRCA pathway and sensitizes head and neck cancer cells to cisplatin. Mol. Cancer 7, 24 (2008).
39. Yarden RI, Brody LC: BRCA1 interacts with components of the histone deacetylase complex. Proc. Natl Acad. Sci. USA 96(9), 4983-4988 (1999).
40. Fabbro M, Savage K, Hobson K et al.: BRCA1-BARD1 complexes are required for p53Ser-15 phosphorylation and a G1/S arrest following ionizing radiation-induced DNA damage. J. Biol. Chem. 279(30), 31251-31258 (2004).
41. Chen J: Ataxia telangiectasia-related protein is involved in the phosphorylation of BRCA1 following deoxyribonucleic acid damage. Cancer Res. 60(18), 5037-5039 (2000).
42. Kim GD, Choi YH, Dimtchev A, Jeong SJ, Dritschilo A, Jung M: Sensing of ionizing radiation-induced DNA damage by ATM through interaction with histone deacetylase. J. Biol. Chem. 274(44), 31127-31130 (1999).
43. Schmidt DR, Schreiber SL: Molecular association between ATR and two components of the nucleosome remodeling and deacetylating complex, HDAC2 and CHD4. Biochemistry 38(44), 14711-14717 (1999).
44. Ju R, Muller MT: Histone deacetylase inhibitors activate p21(WAF1) expression via ATM. Cancer Res. 63(11), 2891-2897 (2003).
45. Vousden KH: p53: death star. Cell 103(5), 691-694 (2000).
46. Ito A, Kawaguchi Y, Lai CH et al.: MDM2-HDAC1-mediated deacetylation of p53 is required for its degradation. EMBO J. 21(22), 6236-6245 (2002).
47. Zhao Y, Lu S, Wu L et al.: Acetylation of p53 at lysine 373/382 by the histone deacetylase inhibitor depsipeptide induces expression of p21(WAF1/CIP1). Mol. Cell. Biol. 26(7), 2782-2790 (2006).
48. Solomon JM, Pasupuleti R, Xu L et al.: Inhibition of SIRT1 catalytic activity increases p53 acetylation but does not alter cell survival following DNA damage. Mol. Cell. Biol. 26(1), 28-38 (2006).
49. Juan LJ, Shia WJ, Chen MH et al.: Histone deacetylases specifically down-regulate p53-dependent gene activation. J. Biol. Chem. 275(27), 20436-20443 (2000).
50. Harms KL, Chen X: Histone deacetylase 2 modulates p53 transcriptional activities through regulation of p53-DNA binding activity. Cancer Res. 67(7), 3145-3152 (2007).
51. Lee JH, Choy ML, Ngo L, Foster SS, Marks PA: Histone deacetylase inhibitor induces DNA damage, which normal but not transformed cells can repair. Proc. Natl Acad. Sci. USA 107(33), 14639-14644 (2010).
52. Conti C, Leo E, Eichler GS et al.: Inhibition of histone deacetylase in cancer cells slows down replication forks, activates dormant origins, and induces DNA damage. Cancer Res. 70(11), 4470-4480 (2010).
53. Sha K, Winn LM: Characterization of valproic acid-initiated homologous recombination. Birth Defects Res. B Dev. Reprod. Toxicol. 89(2), 124-132 (2010).
54. Nitiss JL: Targeting DNA topoisomerase II in cancer chemotherapy. Nat. Rev. Cancer 9(5), 338-350 (2009).
55. Bruzzese F, Rocco M, Castelli S, Di Gennaro E, Desideri A, Budillon A: Synergistic antitumor effect between vorinostat and topotecan in small cell lung cancer cells is mediated by generation of reactive oxygen species and DNA damage-induced apoptosis. Mol. Cancer Ther. 8(11), 3075-3087 (2009).
56. Sarcar B, Kahali S, Chinnaiyan P: Vorinostat enhances the cytotoxic effects of the topoisomerase I inhibitor Sn38 in glioblastoma cell lines. J. Neurooncol. 99(2), 201-207 (2010).
57. Budman DR, Tai J, Calabro A, John V: The histone deacetylase inhibitor panobinostat demonstrates marked synergy with conventional chemotherapeutic agents in human ovarian cancer cell lines. Invest. New Drugs DOI: 10.1007/s10637-010-9467-6 (2010) (Epub ahead of print).
58. Piacentini P, Donadelli M, Costanzo C, Moore PS, Palmieri M, Scarpa A: Trichostatin A enhances the response of chemotherapeutic agents in inhibiting pancreatic cancer cell proliferation. Virchows Arch. 448(6), 797-804 (2006).
59. Daud AI, Dawson J, Deconti RC et al.: Potentiation of a topoisomerase I inhibitor, karenitecin, by the histone deacetylase inhibitor valproic acid in melanoma: translational and Phase I/II clinical trial. Clin. Cancer Res. 15(7), 2479-2487 (2009).
60. Lopez G, Liu J, Ren W et al.: Combining PCI-24781, a novel histone deacetylase inhibitor, with chemotherapy for the treatment of soft tissue sarcoma. Clin. Cancer Res. 15(10), 3472-3483 (2009).
61. Das CM, Aguilera D, Vasquez H et al.: Valproic acid induces p21 and topoisomerase II (α/β) expression and synergistically enhances etoposide cytotoxicity in human glioblastoma cell lines. J. Neurooncol. 85(2), 159-170 (2007).
62. Marchion DC, Bicaku E, Turner JG, Daud AI, Sullivan DM, Munster PN: Synergistic interaction between histone deacetylase and topoisomerase II inhibitors is mediated through topoisomerase IIβ. Clin. Cancer Res. 11(23), 8467-8475 (2005).
63. Johnson CA, Padget K, Austin CA, Turner BM: Deacetylase activity associates with topoisomerase II and is necessary for etoposide-induced apoptosis. J. Biol. Chem. 276(7), 4539-4542 (2001).
64. Tsai SC, Valkov N, Yang WM, Gump J, Sullivan D, Seto E: Histone deacetylase interacts directly with DNA topoisomerase II. Nat. Genet. 26(3), 349-353. (2000).
65. Munster P, Marchion D, Bicaku E et al.: 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. 15(7), 2488-2496 (2009).
66. Adimoolam S, Sirisawad M, Chen J, Thiemann P, Ford JM, Buggy JJ: HDAC inhibitor PCI-24781 decreases RAD51 expression and inhibits homologous recombination. Proc. Natl Acad. Sci. USA 104(49), 19482-19487 (2007).
67. Kim IA, Kim IH, Kim HJ, Chie EK, Kim JS: HDAC inhibitor-mediated radiosensitization in human carcinoma cells: a general phenomenon? J. Radiat. Res. (Tokyo) 51(3), 257-263 (2010).
68. Nome RV, Bratland A, Harman G, Fodstad O, Andersson Y, Ree AH: Cell cycle checkpoint signaling involved in histone deacetylase inhibition and radiation-induced cell death. Mol. Cancer Ther. 4(8), 1231-1238 (2005).
69. Folkvord S, Ree AH, Furre T, Halvorsen T, Flatmark K: Radiosensitization by SAHA in experimental colorectal carcinoma models - in vivo effects and relevance of histone acetylation status. Int. J. Radiat. Oncol. Biol. Phys. 74(2), 546-552 (2009).
70. Camphausen K, Cerna D, Scott T et al.: Enhancement of in vitro and in vivo tumor cell radiosensitivity by valproic acid. Int. J. Cancer 114(3), 380-386 (2005).
71. Camphausen K, Scott T, Sproull M, Tofilon PJ: Enhancement of xenograft tumor radiosensitivity by the histone deacetylase inhibitor MS-275 and correlation with histone hyperacetylation. Clin. Cancer Res. 10(18 Pt 1), 6066-6071 (2004).
72. Kim IA, Shin JH, Kim IH et al.: Histone deacetylase inhibitor-mediated radiosensitization of human cancer cells: class differences and the potential influence of p53. Clin. Cancer Res. 12(3 Pt 1), 940-949 (2006).
73. Ree AH, Dueland S, Folkvord S et al.: Vorinostat, a histone deacetylase inhibitor, combined with pelvic palliative radiotherapy for gastrointestinal carcinoma: the Pelvic Radiation and Vorinostat (PRAVO) Phase 1 study. Lancet Oncol. 11(5), 459-464 (2010).
74. Kavallaris M: Microtubules and resistance to tubulin-binding agents. Nat. Rev. Cancer 10(3), 194-204 (2010).
75. Hubbert C, Guardiola A, Shao R et al.: HDAC6 is a microtubule-associated deacetylase. Nature 417(6887), 455-458 (2002).
76. Marcus AI, O'brate AM, Buey RM et al.: Farnesyltransferase inhibitors reverse taxane resistance. Cancer Res. 66(17), 8838-8846 (2006).
77. Dowdy SC, Jiang S, Zhou XC et al.: Histone deacetylase inhibitors and paclitaxel cause synergistic effects on apoptosis and microtubule stabilization in papillary serous endometrial cancer cells. Mol. Cancer Ther. 5(11), 2767-2776 (2006).
78. Owonikoko TK, Ramalingam SS, Kanterewicz B, Balius TE, Belani CP, Hershberger PA: Vorinostat increases carboplatin and paclitaxel activity in non-small-cell lung cancer cells. Int. J. Cancer 126(3), 743-755 (2010).
79. Kanzaki M, Kakinuma H, Kumazawa T et al.: Low concentrations of the histone deacetylase inhibitor, depsipeptide, enhance the effects of gemcitabine and docetaxel in hormone refractory prostate cancer cells. Oncol. Rep. 17(4), 761-767 (2007).
80. Zhang X, Yashiro M, Ren J, Hirakawa K: Histone deacetylase inhibitor, trichostatin A, increases the chemosensitivity of anticancer drugs in gastric cancer cell lines. Oncol. Rep. 16(3), 563-568 (2006).
81. Chang H, Jeung HC, Jung JJ, Kim TS, Rha SY, Chung HC: Identification of genes associated with chemosensitivity to SAHA/ taxane combination treatment in taxane-resistant breast cancer cells. Breast Cancer Res. Treat. 125(1), 55-63 (2010).
82. Chang H, Rha SY, Jeung HC et al.: Identification of genes related to a synergistic effect of taxane and suberoylanilide hydroxamic acid combination treatment in gastric cancer cells. J. Cancer Res. Clin. Oncol. 136(12), 1901-1913 (2010).
83. Rathkopf D, Wong BY, Ross RW et al.: A Phase I study of oral panobinostat alone and in combination with docetaxel in patients with castration-resistant prostate cancer. Cancer Chemother. Pharmacol. 66(1), 181-189 (2010).
84. Schneider BJ, Kalemkerian GP, Bradley D et al.: Phase I study of vorinostat (suberoylanilide hydroxamic acid, NSC 701852) in combination with docetaxel in patients with advanced and relapsed solid malignancies. Invest. New Drugs DOI: 10.1007/s10637-010-9503-6 (2010) (Epub ahead of print).
85. Lassen U, Molife LR, Sorensen M et al.: A Phase I study of the safety and pharmacokinetics of the histone deacetylase inhibitor belinostat administered in combination with carboplatin and/or paclitaxel in patients with solid tumours. Br. J. Cancer 103(1), 12-17 (2010).
86. 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. 13(12), 3605-3610 (2007).
87. Ramalingam SS, Maitland ML, Frankel P et al.: Carboplatin and paclitaxel in combination with either vorinostat or placebo for first-line therapy of advanced non-small-cell lung cancer. J. Clin. Oncol. 28(1), 56-62 (2010). Randomized, placebo-controlled, double-blind Phase II clinical trial investigating the inclusion of vorinostat into the carboplatin-paclitaxel chemotherapeutic regimen for patients with non-small-cell lung cancer. Results demonstrate a nearly threefold increase in clinical benefit with the inclusion of vorinostat compared with placebo when used in conjunction with carboplatin-paclitaxel in these patients.
88. Noguchi H, Yamashita H, Murakami T et al.: Successful treatment of anaplastic thyroid carcinoma with a combination of oral valproic acid, chemotherapy, radiation and surgery. Endocr. J. 56(2), 245-249 (2009).
89. Merlo A, Herman JG, Mao L et al.: 5′ CpG island methylation is associated with transcriptional silencing of the tumour suppressor p16/CDKN2/MTS1 in human cancers. Nat. Med. 1(7), 686-692 (1995).
90. Dobrovic A, Simpfendorfer D: Methylation of the BRCA1 gene in sporadic breast cancer. Cancer Res. 57(16), 3347-3350 (1997).
91. Kissil JL, Feinstein E, Cohen O et al.: DAP-kinase loss of expression in various carcinoma and B-cell lymphoma cell lines: possible implications for role as tumor suppressor gene. Oncogene 15(4), 403-407 (1997).
92. Bird A: DNA methylation patterns and epigenetic memory. Genes Dev. 16(1), 6-21 (2002).
93. Von Hoff DD, Slavik M, Muggia FM: 5-azacytidine. A new anticancer drug with effectiveness in acute myelogenous leukemia. Ann. Intern. Med. 85(2), 237-245 (1976).
94. Taylor SM, Jones PA: Changes in phenotypic expression in embryonic and adult cells treated with 5-azacytidine. J. Cell. Physiol. 111(2), 187-194 (1982).
95. Taylor SM, Jones PA: Mechanism of action of eukaryotic DNA methyltransferase. Use of 5-azacytosine-containing DNA. J. Mol. Biol. 162(3), 679-692 (1982).
96. Jones PA, Taylor SM: Cellular differentiation, cytidine analogs and DNA methylation. Cell 20(1), 85-93 (1980).
97. Kantarjian H, Issa JP, Rosenfeld CS et al.: Decitabine improves patient outcomes in myelodysplastic syndromes: results of a Phase III randomized study. Cancer 106(8), 1794-1803 (2006).
98. Silverman LR, Demakos EP, Peterson BL et al.: Randomized controlled trial of azacyitidine in patients with the myelodysplastic syndrome: a study of the Cancer and Leukemia Group B. J. Clin. Oncol. 20(10), 2429-2440 (2002).
99. Fenaux P, Mufti GJ, Hellstrom-Lindberg E et al.: Efficacy of azacyitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, Phase III study. Lancet Oncol. 10(3), 223-232 (2009).
100. Van Den Bosch J, Lubbert M, Verhoef G, Wijermans PW: The effects of 5-aza-2′-deoxycytidine (Decitabine) on the platelet count in patients with intermediate and high-risk myelodysplastic syndromes. Leuk. Res. 28(8), 785-790 (2004).
101. Kantarjian H, Oki Y, Garcia-Manero G et al.: Results of a randomized study of 3 schedules of low-dose decitabine in higher-risk myelodysplastic syndrome and chronic myelomonocytic leukemia. Blood 109(1), 52-57 (2007).
102. Griffiths EA, Gore SD: DNA methyltransferase and histone deacetylase inhibitors in the treatment of myelodysplastic syndromes. Semin. Hematol. 45(1), 23-30 (2008).
103. Cameron EE, Bachman KE, Myohanen S, Herman JG, Baylin SB: Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer. Nat. Genet. 21(1), 103-107 (1999).
104. Figueroa ME, Skrabanek L, Li Y et al.: MDS and secondary AML display unique patterns and abundance of aberrant DNA methylation. Blood 114(16), 3448-3458 (2009).
105. Blum W, Klisovic RB, Hackanson B et al.: Phase I study of decitabine alone or in combination with valproic acid in acute myeloid leukemia. J. Clin. Oncol. 25(25), 3884-3891 (2007).
106. Gore SD, Baylin S, Sugar E et al.: Combined DNA methyltransferase and histone deacetylase inhibition in the treatment of myeloid neoplasms. Cancer Res. 66(12), 6361-6369 (2006).
107. Garcia-Manero G, Kantarjian HM, Sanchez-Gonzalez B et al.: Phase I/II study of the combination of 5-aza-2′-deoxycytidine with valproic acid in patients with leukemia. Blood 108(10), 3271-3279 (2006).
108. Soriano AO, Yang H, Faderl S et al.: Safety and clinical activity of the combination of 5-azacytidine, valproic acid, and all-trans retinoic acid in acute myeloid leukemia and myelodysplastic syndrome. Blood 110(7), 2302-2308 (2007).
109. + T-cell response to the MAGE cancer testis antigen by combined treatment with azacyitidine and sodium valproate in patients with acute myeloid leukemia and myelodysplasia. Blood 116(11), 1908-1918 (2010).
110. Voso MT, Santini V, Finelli C et al.: Valproic acid at therapeutic plasma levels may increase 5-azacytidine efficacy in higher risk myelodysplastic syndromes. Clin. Cancer Res. 15(15), 5002-5007 (2009).
111. Maslak P, Chanel S, Camacho LH et al.: Pilot study of combination transcriptional modulation therapy with sodium phenylbutyrate and 5-azacytidine in patients with acute myeloid leukemia or myelodysplastic syndrome. Leukemia 20(2), 212-217 (2006).
112. Braiteh F, Soriano AO, Garcia-Manero G et al.: Phase I study of epigenetic modulation with 5-azacytidine and valproic acid in patients with advanced cancers. Clin. Cancer Res. 14(19), 6296-6301 (2008).
113. Lin J, Gilbert J, Rudek MA et al.: A Phase I dose-finding study of 5-azacytidine in combination with sodium phenylbutyrate in patients with refractory solid tumors. Clin. Cancer Res. 15(19), 6241-6249 (2009).
114. Segura-Pacheco B, Trejo-Becerril C, Perez-Cardenas E et al.: Reactivation of tumor suppressor genes by the cardiovascular drugs hydralazine and procainamide and their potential use in cancer therapy. Clin. Cancer Res. 9(5), 1596-1603 (2003).
115. Arce C, Perez-Plasencia C, Gonzalez-Fierro A et al.: A proof-of-principle study of epigenetic therapy added to neoadjuvant doxorubicin cyclophosphamide for locally advanced breast cancer. PLoS One 1, E98 (2006).
116. Candelaria M, Gallardo-Rincon D, Arce C et al.: A Phase II study of epigenetic therapy with hydralazine and magnesium valproate to overcome chemotherapy resistance in refractory solid tumors. Ann. Oncol. 18(9), 1529-1538 (2007). For patients with solid tumors progressing on chemotherapy, 12 out of 15 exhibited clinical benefit (eight stable disease and four partial response) with the addition of hydralazine and valproate. This combination is currently being evaluated in Phase III trials for ovarian (NCT00533299) and cervical (NCT00532818) cancer.
117. Kim H, Kwon YM, Kim JS et al.: Elevated mRNA levels of DNA methyltransferase-1 as an independent prognostic factor in primary nonsmall cell lung cancer. Cancer 107(5), 1042-1049 (2006).
118. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ: Cancer statistics, 2009. CA Cancer J. Clin. 59(4), 225-249 (2009).
119. Matthews J, Gustafsson JA: Estrogen signaling: a subtle balance between ER α and ER β. Mol. Interv. 3(5), 281-292 (2003).
120. Mangelsdorf Dj, Thummel C, Beato M et al.: The nuclear receptor superfamily: the second decade. Cell 83(6), 835-839 (1995).
121. El-Ashry D, Chrysogelos SA, Lippman ME, Kern FG: Estrogen induction of TGF-α is mediated by an estrogen response element composed of two imperfect palindromes. J. Steroid biochem. Mol. Biol. 59(3-4), 261-269 (1996).
122. Kenny FS, Hui R, Musgrove EA et al.: Overexpression of cyclin D1 messenger RNA predicts for poor prognosis in estrogen receptor-positive breast cancer. Clin. Cancer Res. 5(8), 2069-2076 (1999).
123. Gregory CW, Hamil KG, Kim D et al.: Androgen receptor expression in androgen-independent prostate cancer is associated with increased expression of androgen-regulated genes. Cancer Res. 58(24), 5718-5724 (1998).
124. Amler LC, Agus DB, Leduc C et al.: Dysregulated expression of androgen-responsive and nonresponsive genes in the androgen-independent prostate cancer xenograft model CWR22-R1. Cancer Res. 60(21), 6134-6141 (2000).
125. Coombes RC, Kilburn LS, Snowdon CF et al.: Survival and safety of exemestane versus tamoxifen after 2-3 years' tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial. Lancet 369(9561), 559-570 (2007).
126. Goss PE, Ingle JN, Martino S et al.: Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: updated findings from NCIC CTG MA.17. J. Natl Cancer Inst. 97(17), 1262-1271 (2005).
127. Thurlimann B, Keshaviah A, Coates AS et al.: A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer. N. Engl. J. Med. 353(26), 2747-2757 (2005).
128. Baum M, Budzar AU, Cuzick J et al.: Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trial. Lancet 359(9324), 2131-2139 (2002).
129. Goss PE, Ingle JN, Martino S et al.: A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer. N. Engl. J. Med. 349(19), 1793-1802 (2003).
130. Tammela T: Endocrine treatment of prostate cancer. J. Steroid Biochem. Mol. Biol. 92(4), 287-295 (2004).
131. Bolla M, Collette L, Blank L et al.: Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): a Phase III randomised trial. Lancet 360(9327), 103-106 (2002).
132. Shelley MD, Kumar S, Wilt T, Staffurth J, Coles B, Mason MD: A systematic review and meta-analysis of randomised trials of neo-adjuvant hormone therapy for localised and locally advanced prostate carcinoma. Cancer Treat. Rev. 35(1), 9-17 (2009).
133. Denham JW, Steigler A, Lamb DS et al.: Short-term androgen deprivation and radiotherapy for locally advanced prostate cancer: results from the Trans-Tasman Radiation Oncology Group 96.01 randomised controlled trial. Lancet Oncol. 6(11), 841-850 (2005).
134. Mcleod DG, Iversen P, See WA, Morris T, Armstrong J, Wirth MP: Bicalutamide 150 mg plus standard care vs standard care alone for early prostate cancer. BJU Int. 97(2), 247-254 (2006).
135. Weichert W, Roske A, Gekeler V et al.: Histone deacetylases 1, 2 and 3 are highly expressed in prostate cancer and HDAC2 expression is associated with shorter PSA relapse time after radical prostatectomy. Br. J. Cancer 98(3), 604-610 (2008).
136. Cang S, Feng J, Konno S et al.: Deficient histone acetylation and excessive deacetylase activity as epigenomic marks of prostate cancer cells. Int. J. Oncol. 35(6), 1417-1422 (2009).
137. Zhang Z, Yamashita H, Toyama T et al.: Quantitation of HDAC1 mRNA expression in invasive carcinoma of the breast. Breast Cancer Res. Treat. 94(1), 11-16 (2005).
138. 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. 90(1), 15-23 (2005).
139. Reid G, Metivier R, Lin CY et al.: Multiple mechanisms induce transcriptional silencing of a subset of genes, including oestrogen receptor α, in response to deacetylase inhibition by valproic acid and trichostatin A. Oncogene 24(31), 4894-4907 (2005).
140. Bicaku E, Marchion DC, Schmitt M, Munster PN: Selective inhibition of histone deacetylase 2 silences progesterone receptor mediated signaling. Cancer Res. 68(5), 1513-1519 (2008). First preclinical work to demonstrate that histone deacetylase inhibition potentiates the antitumor activity of the selective estrogen receptor modulator tamoxifen in estrogen receptor-positive breast cancer cell lines.
141. Alao JP, Lam EW, Ali S et al.: Histone deacetylase inhibitor trichostatin a represses estrogen receptor α-dependent transcription and promotes proteasomal degradation of cyclin D1 in human breast carcinoma cell lines. Clin. Cancer Res. 10(23), 8094-8104 (2004).
142. 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. 66(12), 6370-6378 (2006).
143. Yang X, Phillips DL, Ferguson AT, Nelson WG, Herman JG, Davidson NE: Synergistic activation of functional estrogen receptor (ER)-α by DNA methyltransferase and histone deacetylase inhibition in human ER-α-negative breast cancer cells. Cancer Res. 61(19), 7025-7029 (2001).
144. Fan J, Yin WJ, Lu JS et al.: ER α negative breast cancer cells restore response to endocrine therapy by combination treatment with both HDAC inhibitor and DNMT inhibitor. J. Cancer Res. Clin. Oncol. 134(8), 883-890 (2008).
145. Fiskus W, Ren Y, Mohapatra A et al.: Hydroxamic acid analogue histone deacetylase inhibitors attenuate estrogen receptor-α levels and transcriptional activity: a result of hyperacetylation and inhibition of chaperone function of heat shock protein 90. Clin. Cancer Res. 13(16), 4882-4890 (2007).
146. Fu M, Rao M, Wu K et al.: The androgen receptor acetylation site regulates camp and AKT but not ERK-induced activity. J. Biol. Chem. 279(28), 29436-29449 (2004).
147. Fu M, Wang C, Wang J et al.: Androgen receptor acetylation governs trans activation and MEKK1-induced apoptosis without affecting in vitro sumoylation and trans-repression function. Mol. Cell. Biol. 22(10), 3373-3388 (2002).
148. Wang C, Fu M, Angeletti RH et al.: Direct acetylation of the estrogen receptor α hinge region by p300 regulates transactivation and hormone sensitivity. J. Biol. Chem. 276(21), 18375-18383 (2001).
149. Fuqua SA, Wiltschke C, Zhang QX et al.: A hypersensitive estrogen receptor-α mutation in premalignant breast lesions. Cancer Res. 60(15), 4026-4029 (2000).
150. Welsbie DS, Xu J, Chen Y et al.: Histone deacetylases are required for androgen receptor function in hormone-sensitive and castrate-resistant prostate cancer. Cancer Res. 69(3), 958-966 (2009).
151. Rhodes DR, Kalyana-Sundaram S, Mahavisno V, Barrette TR, Ghosh D, Chinnaiyan AM: Mining for regulatory programs in the cancer transcriptome. Nat. Genet. 37(6), 579-583 (2005).
152. Khanim FL, Gommersall LM, Wood VH et al.: Altered SMRT levels disrupt vitamin D3 receptor signalling in prostate cancer cells. Oncogene 23(40), 6712-6725 (2004).
153. Battaglia S, Maguire O, Thorne JL et al.: Elevated NCOR1 disrupts PPARα/γ signaling in prostate cancer and forms a targetable epigenetic lesion. Carcinogenesis 31(9), 1650-1660 (2010).
154. Liu X, Gomez-Pinillos A, Liu X, Johnson EM, Ferrari AC: Induction of bicalutamide sensitivity in prostate cancer cells by an epigenetic PURα-mediated decrease in androgen receptor levels. Prostate 70(2), 179-189 (2010).
155. 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. 14(21), 7138-7142 (2008).
156. 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. 105(3), 297-309 (2007).
157. Munster PN, Lacevic M, Schmitt M et al.: Phase II trial of the HDAC inhibitor, vorinostat, in combination with tamoxifen in women with ER-positive breast cancer who failed prior aromatase inhibitors. J. Clin. Oncol. 26(Suppl.), 3501 (2008).
158. Molife LR, Attard G, Fong PC et al.: Phase II, two-stage, single-arm trial of the histone deacetylase inhibitor (HDACi) romidepsin in metastatic castration-resistant prostate cancer (CRPC). Ann. Oncol. 21(1), 109-113 (2010).
159. Bradley D, Rathkopf D, Dunn R et al.: Vorinostat in advanced prostate cancer patients progressing on prior chemotherapy (National Cancer Institute Trial 6862): trial results and interleukin-6 analysis: a study by the Department of Defense Prostate Cancer Clinical Trial Consortium and University of Chicago Phase 2 Consortium. Cancer 115(23), 5541-5549 (2009).
160. Bjorkman M, Iljin K, Halonen P et al.: Defining the molecular action of HDAC inhibitors and synergism with androgen deprivation in ERG-positive prostate cancer. Int. J. Cancer 123(12), 2774-2781 (2008).
161. Pfeiffer MJ, Mulders PF, Schalken JA: An in vitro model for preclinical testing of endocrine therapy combinations for prostate cancer. Prostate 70(14), 1524-1532 (2010).
162. Marrocco DL, Tilley WD, Bianco-Miotto T et al.: Suberoylanilide hydroxamic acid (vorinostat) represses androgen receptor expression and acts synergistically with an androgen receptor antagonist to inhibit prostate cancer cell proliferation. Mol. Cancer Ther. 6(1), 51-60 (2007).
163. Barros FF, Powe DG, Ellis IO, Green AR: Understanding the HER family in breast cancer: interaction with ligands, dimerization and treatments. Histopathology 56(5), 560-572 (2010).
164. Lurje G, Lenz HJ: EGFR signaling and drug discovery. Oncology 77(6), 400-410 (2009).
165. Hu J, Colburn NH: Histone deacetylase inhibition down-regulates cyclin D1 transcription by inhibiting nuclear factor-κB/p65 DNA binding. Mol. Cancer Res. 3(2), 100-109 (2005).
166. Alao JP, Stavropoulou AV, Lam EW, Coombes RC, Vigushin DM: Histone deacetylase inhibitor, trichostatin A induces ubiquitin-dependent cyclin D1 degradation in MCF-7 breast cancer cells. Mol. Cancer 5, 8 (2006).
167. Fu M, Rao M, Bouras T et al.: Cyclin D1 inhibits peroxisome proliferator-activated receptor γ-mediated adipogenesis through histone deacetylase recruitment. J. Biol. Chem. 280(17), 16934-16941 (2005).
168. Conte P, Campone M, Pronzato P et al.: Phase I trial of panobinostat (LBH589) in combination with trastuzumab in pretreated HER2-positive metastatic breast cancer (MBC): preliminary safety and tolerability results. J. Clin. Oncol. 27(15 Suppl.), 1081 (2009).
169. Witta SE, Dziadziuszko R, Yoshida K et al.: ErbB-3 expression is associated with E-cadherin and their coexpression restores response to gefitinib in non-small-cell lung cancer (NSCLC). Ann. Oncol. 20(4), 689-695 (2009). Treatment of non-small-cell lung cancer cells with vorinostat and entinostat increased E-cadherin and ErbB-3 levels, whose expression increased gefitinib-induced cell death. Vorinostat synergistically enhanced gefitinib-mediated cell death in gefitinib-resistant cell lines.
170. Witta SE, Gemmill RM, Hirsch FR et al.: Restoring E-cadherin expression increases sensitivity to epidermal growth factor receptor inhibitors in lung cancer cell lines. Cancer Res. 66(2), 944-950 (2006).
171. Baradari V, Hopfner M, Huether A, Schuppan D, Scherubl H: Histone deacetylase inhibitor MS-275 alone or combined with bortezomib or sorafenib exhibits strong antiproliferative action in human cholangiocarcinoma cells. World J. Gastroenterol. 13(33), 4458-4466 (2007).
172. Zhang G, Park MA, Mitchell C et al.: Vorinostat and sorafenib synergistically kill tumor cells via flip suppression and CD95 activation. Clin. Cancer Res. 14(17), 5385-5399 (2008).
173. Haberland M, Johnson A, Mokalled MH, Montgomery RL, Olson EN: Genetic dissection of histone deacetylase requirement in tumor cells. Proc. Natl Acad. Sci. USA 106(19), 7751-7755 (2009). Histone deacetylases 1 and 2 have redundant functions in tumor growth, and select depletion of both causes a significant reduction in tumor volume in vivo.
174. Oehme I, Deubzer HE, Wegener D et al.: Histone deacetylase 8 in neuroblastoma tumorigenesis. Clin. Cancer Res. 15(1), 91-99 (2009).
175. National Cancer Institute World Community Grid www.cancer.gov
176. NIH clinical trial database www.clinicaltrials.gov
177. National Comprehensive Cancer Network www.NCCN.org