Histone deacetylase inhibitors: Current status and overview of recent clinical trials

Drugs

Volumn 69, Issue 14, 2009, Pages 1911-1934

  Ma, Xujun ^a   Ezzeldin, Hany H ^a   Diasio, Robert B ^a  

^a MAYO GRADUATE SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

3 PHENYLSULFAMOYLCINNAMOHYDROXAMIC ACID; 4 [N (2 HYDROXYETHYL) N [2 (3 INDOLYL)ETHYL]AMINOMETHYL]CINNAMOHYDROXAMIC ACID; 4 N ACETYLDINALINE; 4 PHENYLBUTYRIC ACID; 6 CYCLOHEXYLMETHOXY 2 (4 SULFAMOYLANILINO)PURINE; 7 HYDROXYSTAUROSPORINE; BACECA; BUTYRIC ACID; CAPECITABINE; CARBOPLATIN; EPIRUBICIN; GIVINOSTAT; HISTONE ACETYLTRANSFERASE; HISTONE DEACETYLASE; HISTONE DEACETYLASE INHIBITOR; HYDRALAZINE; ITF 2357; N (2 AMINOPHENYL) 4 (3 PYRIDINYLMETHOXYCARBONYLAMINOMETHYL)BENZAMIDE; N (2 AMINOPHENYL) 4 [4 (3 PYRIDINYL) 2 PYRIMIDINYLAMINOMETHYL]BENZAMIDE; OXAMFLATIN; PACLITAXEL; PANOBINOSTAT; PARTHENOLIDE; PCI 24781; PIVALOYLOXYMETHYL BUTYRATE; PYROXAMIDE; ROMIDEPSIN; ROSCOVITINE; SAVICOL; TRICHOSTATIN A; UNCLASSIFIED DRUG; UNINDEXED DRUG; VALPROATE MAGNESIUM; VALPROIC ACID; VORINOSTAT;

ABDOMINAL PAIN; ACETYLATION; AMINOTRANSFERASE BLOOD LEVEL; ANEMIA; ANOREXIA; ANTIANGIOGENIC ACTIVITY; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ASTHENIA; CANCER CELL CULTURE; CANCER COMBINATION CHEMOTHERAPY; CANCER THERAPY; CELL CYCLE ARREST; CLINICAL TRIAL; CONFUSION; CONSTIPATION; DEACETYLATION; DEHYDRATION; DIARRHEA; DIZZINESS; DNA METHYLATION; DRUG EFFICACY; DRUG MECHANISM; DRUG TOLERABILITY; DYSGEUSIA; DYSPEPSIA; DYSPNEA; EPIGENETICS; FATIGUE; FEVER; FLUSHING; GLIOMA; HEADACHE; HEART VENTRICLE TACHYCARDIA; HUMAN; HYPERGLYCEMIA; HYPOALBUMINEMIA; HYPOKALEMIA; HYPONATREMIA; HYPOPHOSPHATEMIA; LEUKEMIA; LEUKOPENIA; LUNG CANCER; LUNG NON SMALL CELL CANCER; LYMPHOCYTOPENIA; LYMPHOMA; MUCOSA INFLAMMATION; MULTIPLE CYCLE TREATMENT; MYELODYSPLASTIC SYNDROME; NAUSEA; NEOPLASM; NEUROENDOCRINE TUMOR; NEUROLOGIC DISEASE; NEUTROPENIA; OUTCOME ASSESSMENT; PERICARDIAL EFFUSION; PROTEIN INDUCTION; QT PROLONGATION; REVIEW; SIDE EFFECT; SINUS TACHYCARDIA; SOLID TUMOR; SOMNOLENCE; ST SEGMENT; T CELL LYMPHOMA; THROMBOCYTOPENIA; VERTIGO; VOMITING;

ACETYLATION; ANTINEOPLASTIC AGENTS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CLINICAL TRIALS AS TOPIC; ENZYME INHIBITORS; EPIGENESIS, GENETIC; FORECASTING; GENE EXPRESSION; HISTONE ACETYLTRANSFERASES; HISTONE DEACETYLASES; HUMANS; MODELS, BIOLOGICAL; NEOPLASMS;

EID: 70349100446     PISSN: 00126667     EISSN: 11791950     Source Type: Journal    
DOI: 10.2165/11315680-000000000-00000     Document Type: Review

References (158)

1. 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 2008 Feb 1; 111 (3): 1060-1066
2. Klimek VM, Fircanis S, Maslak P, et al. Tolerability, pharmacodynamics, and pharmacokinetics studies of depsipeptide (romidepsin) in patients with acute myelo-genous leukemia or advanced myelodysplastic syndromes. Clin Cancer Res 2008 Feb 1; 14 (3): 826-832
3. Byrd JC, Marcucci G, Parthun MR, et al. A phase 1 and pharmacodynamic study of depsipeptide (FK228) in chronic lymphocytic leukemia and acute myeloid leukemia. Blood 2005 Feb 1; 105 (3): 959-967
4. 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 2007 Sep 1; 25 (25): 3884-3891
5. Piekarz RL, Sackett DL, Bates SE. Histone deacetylase inhibitors and demethylating agents: clinical development of histone deacetylase inhibitors for cancer therapy. Cancer J 2007 Jan-Feb; 13 (1): 30-39
6. Shen L, Issa JP. Epigenetics in colorectal cancer. Curr Opin Gastroenterol 2002 Jan; 18 (1): 68-73
7. Agrawal A, Murphy RF, Agrawal DK. DNA methylation in breast and colorectal cancers. Mod Pathol 2007 Jul; 20 (7): 711-721
8. Mariadason JM. HDACs and HDAC inhibitors in colon cancer. Epigenetics 2008 Jan-Feb; 3 (1): 28-37
9. Glozak MA, Seto E. Histone deacetylases and cancer. Oncogene 2007 Aug 13; 26 (37): 5420-5432
10. Toyota M, Suzuki H, Yamashita T, et al. Cancer epige-nomics: implications of DNA methylation in personalized cancer therapy. Cancer Sci 2009 May; 100 (5): 787-791
11. Mahlknecht U, Hoelzer D. Histone acetylation modifiers in the pathogenesis of malignant disease. Mol Med 2000 Aug; 6 (8): 623-644
12. Santos-Rosa H, Caldas C. Chromatin modifier enzymes, the histone code and cancer. Eur J Cancer 2005 Nov; 41 (16): 2381-2402
13. Jones PA, Baylin SB. The epigenomics of cancer. Cell 2007 Feb 23; 128 (4): 683-692
14. Fraga MF, Ballestar E, Villar-Garea A, et al. Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer. Nat Genet 2005 Apr; 37 (4): 391-400
15. Lafon-Hughes L, Di Tomaso MV, Mendez-Acuna L, et al. Chromatin- remodelling mechanisms in cancer. Mutat Res 2008 Mar-Apr; 658 (3): 191-214
16. Ishihama K, Yamakawa M, Semba S, et al. Expression of HDAC1 and CBP/p300 in human colorectal carcinomas. J Clin Pathol 2007 Nov; 60 (11): 1205-1210
17. Yang XJ, Seto E. HATs and HDACs: from structure, function and regulation to novel strategies for therapy and prevention. Oncogene 2007 Aug 13; 26 (37): 5310-5318
18. Acharya MR, Sparreboom A, Venitz J, et al. Rational development of histone deacetylase inhibitors as anticancer agents: a review. Mol Pharmacol 2005 Oct; 68 (4): 917-932
19. Iyer NG, Ozdag H, Caldas C. p300/CBP and cancer. On-cogene 2004 May 24; 23 (24): 4225-4231
20. Kitabayashi I, Aikawa Y, Yokoyama A, et al. Fusion of MOZ and p300 histone acetyltransferases in acute monocytic leukemia with a t(8;22)(p11;q13) chromosome translocation. Leukemia 2001 Jan; 15 (1): 89-94
21. Rozman M, Camos M, Colomer D, et al. Type I MOZ/CBP (MYST3/CREBBP) is the most common chi-meric transcript in acute myeloid leukemia with t(8;16)(p11;p13) translocation. Genes Chromosomes Cancer 2004 Jun; 40 (2): 140-145
22. Crowley JA, Wang Y, Rapoport AP, et al. Detection of MOZ-CBP fusion in acute myeloid leukemia with 8;16 translocation. Leukemia 2005 Dec; 19 (12): 2344-2345
23. Egger G, Liang G, Aparicio A, et al. Epigenetics in human disease and prospects for epigenetic therapy. Nature 2004 May 27; 429 (6990): 457-463
24. Xu WS, Parmigiani RB, Marks PA. Histone deacetylase inhibitors: molecular mechanisms of action. Oncogene 2007 Aug 13; 26 (37): 5541-5552
25. Carew JS, Giles FJ, Nawrocki ST. Histone deacetylase inhibitors: mechanisms of cell death and promise in combination cancer therapy. Cancer Lett 2008 Sep 28; 269 (1): 7-17
26. Dokmanovic M, Clarke C, Marks PA. Histone deacetylase inhibitors: overview and perspectives. Mol Cancer Res 2007 Oct; 5 (10): 981-989 (Pubitemid 350080267)
27. Bolden JE, Peart MJ, Johnstone RW. Anticancer activities of histone deacetylase inhibitors. Nat Rev Drug Disc 2006 Sep; 5 (9): 769-784
28. Dokmanovic M, Marks PA. Prospects: histone deacetylase inhibitors. J Cell Biochem 2005 Oct 1; 96 (2): 293-304
29. Fouladi M. Histone deacetylase inhibitors in cancer therapy. Cancer Invest 2006 Aug-Sep; 24 (5): 521-527
30. Mann BS, Johnson JR, Cohen MH, et al. FDA approval summary: vorinostat for treatment of advanced primary cutaneous T-cell lymphoma. Oncologist 2007 Oct; 12 (10): 1247-1252
31. Glaser KB. HDAC inhibitors: clinical update and mechanism-based potential. Biochem Pharmacol 2007 Sep 1; 74 (5): 659-671
32. Duvic M, Talpur R, Ni X, et al. Phase 2 trial of oral vorinostat (suberoylanilide hydroxamic acid, SAHA) for refractory cutaneous T-cell lymphoma (CTCL). Blood 2007 Jan 1; 109 (1): 31-39 (Pubitemid 46053039)
33. Crump M, Coiffier B, Jacobsen ED, et al. Phase II trial of oral vorinostat (suberoylanilide hydroxamic acid) in relapsed diffuse large-B-cell lymphoma. Ann Oncol 2008 May; 19 (5): 964-969
34. Modesitt SC, Sill M, Hoffman JS, et al. A phase II study of vorinostat in the treatment of persistent or recurrent epithelial ovarian or primary peritoneal carcinoma: a Gynecol Oncol Group study. Gynecol Oncol 2008 May; 109 (2): 182-186
35. Vansteenkiste J, Van Cutsem E, Dumez H, et al. Early phase II trial of oral vorinostat in relapsed or refractory breast, colorectal, or non-small cell lung cancer. Invest New Drugs 2008 Oct; 26 (5): 483-488
36. Blumenschein Jr GR, Kies MS, Papadimitrakopoulou VA, et al. Phase II trial of the histone deacetylase inhibitor vorinostat (Zolinza, suberoylanilide hydroxamic acid, SAHA) in patients with recurrent and/or metastatic head and neck cancer. Invest New Drugs 2008 Feb; 26 (1): 81-87
37. 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 Jun 10; 23 (17): 3923-3931
38. Steele NL, Plumb JA, Vidal L, et al. A phase 1 pharmacokinetic and pharmacodynamic study of the histone deacetylase inhibitor belinostat in patients with advanced solid tumors. Clin Cancer Res 2008 Feb 1; 14 (3): 804-810
39. De Bono JS, Kristeleit R, Tolcher A, et al. Phase I pharmacokinetic and pharmacodynamic study of LAQ824, a hydroxamate histone deacetylase inhibitor with a heat shock protein-90 inhibitory profile, in patients with advanced solid tumors. Clin Cancer Res 2008 Oct 15; 14 (20): 6663-6673
40. Giles F, Fischer T, Cortes J, et al. A phase I study of intravenous LBH589, a novel cinnamic hydroxamic acid analogue histone deacetylase inhibitor, in patients with refractory hematologic malignancies. Clin Cancer Res 2006 Aug 1; 12 (15): 4628-4635
41. Viviani S, Bonfante V, Fasola C, et al. Phase II study of the histone-deacetylase inhibitor ITF2357 in relapsed/ refractory Hodgkin's lymphoma patients [abstract no. 0.8532]. 2008 Annual Meeting Proceedings of the American Society of Clinical Oncology (ASCO); 2008 May 30-Jun 3; Chicago (IL)
42. Prince HM, Bishton M, Harrison S. The potential of histone deacetylase inhibitors for the treatment of multiple myeloma. Leuk Lymphoma 2008 Mar; 49 (3): 385-387
43. Shah MH, Binkley P, Chan K, et al. Cardiotoxicity of histone deacetylase inhibitor depsipeptide in patients with metastatic neuroendocrine tumors. Clin Cancer Res 2006 Jul 1; 12 (13): 3997-4003
44. Fouladi M, Furman WL, Chin T, et al. Phase I study of depsipeptide in pediatric patients with refractory solid tumors: a Children's Oncology Group report. J Clin Oncol 2006 Aug 1; 24 (22): 3678-3685
45. Schrump DS, Fischette MR, Nguyen DM, et al. Clinical and molecular responses in lung cancer patients receiving Romidepsin. Clin Cancer Res 2008 Jan 1; 14 (1): 188-198
46. Patnaik A, Rowinsky EK, Villalona MA, et al. A phase I study of pivaloyloxymethyl butyrate, a prodrug of the differentiating agent butyric acid, in patients with advanced solid malignancies. Clin Cancer Res 2002 Jul; 8 (7): 2142-2148
47. Reid T, Valone F, Lipera W, et al. Phase II trial of the histone deacetylase inhibitor pivaloyloxymethyl butyrate (Pivanex, AN-9) in advanced non-small cell lung cancer. Lung Cancer 2004 Sep; 45 (3): 381-386
48. Carducci MA, Gilbert J, Bowling MK, et al. A phase I clinical and pharmacological evaluation of sodium phenylbutyrate on an 120-h infusion schedule. Clin Cancer Res 2001 Oct; 7 (10): 3047-3055
49. Gilbert J, Baker SD, Bowling MK, et al. A phase I dose escalation and bioavailability study of oral sodium phenylbutyrate in patients with refractory solid tumor malignancies. Clin Cancer Res 2001 Aug; 7 (8): 2292-2300
50. Phuphanich S, Baker SD, Grossman SA, et al. Oral sodium phenylbutyrate in patients with recurrent malignant gliomas: a dose escalation and pharmacologic study. Neuro Oncol 2005 Apr; 7 (2): 177-182
51. Camacho LH, Olson J, Tong WP, et al. Phase I dose escalation clinical trial of phenylbutyrate sodium administered twice daily to patients with advanced solid tumors. Invest New Drugs 2007 Apr; 25 (2): 131-138
52. Atmaca A, Al-Batran SE, Maurer A, et al. Valproic acid (VPA) in patients with refractory advanced cancer: a dose escalating phase I clinical trial. Br J Cancer 2007 Jul 16; 97 (2): 177-182
53. Kummar S, Gutierrez M, Gardner ER, et al. Phase I trial of MS-275, a histone deacetylase inhibitor, administered weekly in refractory solid tumors and lymphoid malignancies. Clin Cancer Res 2007 Sep 15; 13 (18 Pt 1): 5411-5417
54. Gore L, Rothenberg ML, O'Bryant CL, et al. A phase I and pharmacokinetic study of the oral histone deacetylase inhibitor, MS-275, in patients with refractory solid tumors and lymphomas. Clin Cancer Res 2008 Jul 15; 14 (14): 4517-4525
55. Prakash S, Foster BJ, Meyer M, et al. Chronic oral administration of CI-994: a phase 1 study. InvestNew Drugs 2001; 19 (1): 1-11
56. Siu LL, Pili R, Duran I, et al. Phase I study of MGCD0103 given as a three-times-per-week oral dose in patients with advanced solid tumors. J Clin Oncol 2008 Apr 20; 26 (12): 1940-1947
57. Garcia-Manero G, Assouline S, Cortes J, et al. Phase 1 study of the oral isotype specific histone deacetylase inhibitor MGCD0103 in leukemia. Blood 2008 Aug 15; 112 (4): 981-989
58. Insinga A, Monestiroli S, Ronzoni S, et al. Inhibitors of histone deacetylases induce tumor-selective apoptosis through activation of the death receptor pathway. Nature Med 2005 Jan; 11 (1): 71-76
59. Edwards A, Li J, Atadja P, et al. Effect of the histone deacetylase inhibitor LBH589 against epidermal growth factor receptor-dependent human lung cancer cells. Mol Cancer Ther 2007 Sep; 6 (9): 2515-2524
60. Xu W, Ngo L, Perez G, et al. Intrinsic apoptotic and thioredoxin pathways in human prostate cancer cell response to histone deacetylase inhibitor. Proc Natl Acad Sci U S A 2006 Oct 17; 103 (42): 15540-15545
61. Inoue S, Riley J, Gant TW, et al. Apoptosis induced by histone deacetylase inhibitors in leukemic cells is mediated by Bim and Noxa. Leukemia 2007 Aug; 21 (8): 1773-1782
62. Rosato RR, Maggio SC, Almenara JA, et al. The histone deacetylase inhibitor LAQ824 induces human leukemia cell death through a process involving XIAP downregulation, oxidative injury, and the acid sphingomyelinase- dependent generation of ceramide. Mol Pharmacol 2006 Jan; 69 (1): 216-225
63. Butler LM, Zhou X, Xu WS, et al. The histone deacetylase inhibitor SAHA arrests cancer cell growth, up-regulates thioredoxin-binding protein-2, and down-regulates thioredoxin. Proc Natl Acad Sci U S A 2002 Sep 3; 99 (18): 11700-11705
64. Chen G, Li A, Zhao M, et al. Proteomic analysis identifies protein targets responsible for depsipeptide sensitivity in tumor cells. J Proteome Res 2008 Jul; 7 (7): 2733-2742
65. Noh EJ, Lee JS. Functional interplay between modulation of histone deacetylase activity and its regulatory role in G2-M transition. Biochem Biophys Res Commun 2003 Oct 17; 310 (2): 267-273
66. Qian X, Ara G, Mills E, et al. Activity of the histone deacetylase inhibitor belinostat (PXD101) in preclinical models of prostate cancer. Int J Cancer 2008 Mar 15; 122 (6): 1400-1410
67. Cheng YC, Lin H, Huang MJ, et al. Downregulation of c- Myc is critical for valproic acid-induced growth arrest and myeloid differentiation of acute myeloid leukemia. Leuk Res 2007 Oct; 31 (10): 1403-1411
68. Komatsu N, Kawamata N, Takeuchi S, et al. SAHA, a HDAC inhibitor, has profound anti-growth activity against non-small cell lung cancer cells. Oncol Rep 2006 Jan; 15 (1): 187-191
69. Valentini A, Gravina P, Federici G, et al. Valproic acid induces apoptosis, p16INK4A upregulation and sensitization to chemotherapy in humanmelanoma cells. Cancer Biol Ther 2007 Feb; 6 (2): 185-191
70. Sakajiri S, Kumagai T, Kawamata N, et al. Histone deacetylase inhibitors profoundly decrease proliferation of human lymphoid cancer cell lines. Exp Hematol 2005 Jan; 33 (1): 53-61
71. Gui CY, Ngo L, Xu WS, et al. Histone deacetylase (HDAC) inhibitor activation of p21WAF1 involves changes in promoter-associated proteins, including HDAC1. Proc Natl Acad Sci U S A 2004 Feb 3; 101 (5): 1241-1246
72. Alao JP, Stavropoulou AV, Lam EW, et al. Histone deacetylase inhibitor, trichostatin A induces ubiquitindependent cyclin D1 degradation in MCF-7 breast cancer cells. Mol Cancer 2006; 5: 8
73. Qian DZ, Kato Y, Shabbeer S, et al. Targeting tumor angiogenesis with histone deacetylase inhibitors: the hydroxamic acid derivative LBH589. Clin Cancer Res 2006 Jan 15; 12 (2): 634-642
74. Kim MS, Kwon HJ, Lee YM, et al. Histone deacetylases induce angiogenesis by negative regulation of tumor suppressor genes. Nature Med 2001 Apr; 7 (4): 437-443
75. Kang JH, Kim MJ, Chang SY, et al. CCAAT box is required for the induction of human thrombospondin-1 gene by trichostatin A. J Cell Biochem 2008 Jul 1; 104 (4): 1192-1203
76. Kwon HJ, Kim MS, Kim MJ, et al. Histone deacetylase inhibitor FK228 inhibits tumor angiogenesis. Int J Cancer 2002 Jan 20; 97 (3): 290-296
77. Mie Lee Y, Kim SH, Kim HS, et al. Inhibition of hypoxiainduced angiogenesis by FK228, a specific histone deacetylase inhibitor, via suppression of HIF-1alpha activity. Biochem Biophys Res Commun 2003 Jan 3; 300 (1): 241-246
78. Chinnaiyan P, Varambally S, Tomlins SA, et al. Enhancing the antitumor activity of ErbB blockade with histone deacetylase (HDAC) inhibition. Int J Cancer 2006 Feb 15; 118 (4): 1041-1050
79. Sasakawa Y, Naoe Y, Noto T, et al. Antitumor efficacy of FK228, a novel histone deacetylase inhibitor, depends on the effect on expression of angiogenesis factors. Biochem Pharmacol 2003 Sep 15; 66 (6): 897-906
80. Zgouras D, Becker U, Loitsch S, et al. Modulation of angiogenesis-related protein synthesis by valproic acid. Biochem Biophys Res Commun 2004 Apr 9; 316 (3): 693-697
81. Deroanne CF, Bonjean K, Servotte S, et al. Histone deacetylases inhibitors as anti-angiogenic agents altering vascular endothelial growth factor signaling. Oncogene 2002 Jan 17; 21 (3): 427-436
82. Joseph J, Mudduluru G, Antony S, et al. Expression profiling of sodium butyrate (NaB)-treated cells: identification of regulation of genes related to cytokine signaling and cancer metastasis by NaB. Oncogene 2004 Aug 19; 23 (37): 6304-6315
83. Mazieres J, Tovar D, He B, et al. Epigenetic regulation of RhoB loss of expression in lung cancer. BMC Cancer 2007; 7: 220
84. Liu LT, Chang HC, Chiang LC, et al. Histone deacetylase inhibitor up-regulates RECK to inhibit MMP-2 activation and cancer cell invasion. Cancer Res 2003 Jun 15; 63 (12): 3069-3072
85. Xu WS, Perez G, Ngo L, et al. Induction of polyploidy by histone deacetylase inhibitor: a pathway for antitumor effects. Cancer Research 2005 Sep 1; 65 (17): 7832-7839
86. Stevens FE, Beamish H, Warrener R, et al. Histone deacetylase inhibitors induce mitotic slippage. Oncogene 2008 Feb 28; 27 (10): 1345-1354
87. Magnaghi-Jaulin L, Eot-Houllier G, Fulcrand G, et al. Histone deacetylase inhibitors induce premature sister chromatid separation and override the mitotic spindle assembly checkpoint. Cancer Res 2007 Jul 1; 67 (13): 6360-6367
88. Chen CL, Sung J, Cohen M, et al. Valproic acid inhibits invasiveness in bladder cancer but not in prostate cancer cells. J Pharmacol Exp Ther 2006 Nov; 319 (2): 533-542 (Pubitemid 44776356)
89. Peart MJ, Tainton KM, Ruefli AA, et al. Novel mechanisms of apoptosis induced by histone deacetylase inhibitors. Cancer Res 2003 Aug 1; 63 (15): 4460-4471
90. Domingo-Domenech J, Pippa R, Tapia M, et al. Inactivation of NF-kappaB by proteasome inhibition contributes to increased apoptosis induced by histone deacetylase inhibitors in human breast cancer cells. Breast Cancer Res Treat 2008 Nov; 112 (1): 53-62
91. Dai Y, Rahmani M, Dent P, et al. Blockade of histone deacetylase inhibitor-induced RelA/p65 acetylation and NF-kappaB activation potentiates apoptosis in leukemia cells through a process mediated by oxidative damage, XIAP downregulation, and c-Jun N-terminal kinase 1 activation. Mol Cell Biol 2005 Jul; 25 (13): 5429-5444
92. Inoue S, Walewska R, Dyer MJ, et al. Downregulation of Mcl-1 potentiates HDAC inhibitors-mediated apoptosis in leukemic cells. Leukemia 2008 Apr; 22 (4): 819-825
93. Yeow WS, Ziauddin MF, Maxhimer JB, et al. Potentiation of the anticancer effect of valproic acid, an antiepileptic agent with histone deacetylase inhibitory activity, by the kinase inhibitor Staurosporine or its clinically relevant analogue UCN-01. Br J Cancer 2006 May 22; 94 (10): 1436-1445
94. Ungerstedt JS, Sowa Y, Xu WS, et al. Role of thioredoxin in the response of normal and transformed cells to histone deacetylase inhibitors. Proc Natl Acad Sci U S A 2005 Jan 18; 102 (3): 673-678
95. Fotheringham S, Epping MT, Stimson L, et al. Genomewide loss-of-function screen reveals an important role for the proteasome in HDAC inhibitor-induced apoptosis. Cancer Cell 2009 Jan 6; 15 (1): 57-66
96. Pei XY, Dai Y, Grant S. Synergistic induction of oxidative injury and apoptosis in human multiple myeloma cells by the proteasome inhibitor bortezomib and histone deacetylase inhibitors. Clin Cancer Res 2004 Jun 1; 10 (11): 3839-3852
97. Heider U, von Metzler I, Kaiser M, et al. Synergistic interaction of the histone deacetylase inhibitor SAHA with the proteasome inhibitor bortezomib in mantle cell lymphoma. Eur J Haematol 2008 Feb; 80 (2): 133-142
98. Miller CP, Ban K, Dujka ME, et al. NPI-0052, a novel proteasome inhibitor, induces caspase-8 and ROSdependent apoptosis alone and in combination with HDAC inhibitors in leukemia cells. Blood 2007 Jul 1; 110 (1): 267-277
99. Dai Y, Chen S, Kramer LB, et al. Interactions between bortezomib and romidepsin and belinostat in chronic lymphocytic leukemia cells. Clin Cancer Res 2008 Jan 15; 14 (2): 549-558
100. Miller CP, Rudra S, Keating MJ, et al. Caspase-8 dependent histone acetylation by a novel proteasome inhibitor, NPI-0052: a mechanism for synergy in leukemia cells. Blood 2009 Apr 30; 113 (18): 4289-4299
101. Emanuele S, Lauricella M, Carlisi D, et al. SAHA induces apoptosis in hepatoma cells and synergistically interacts with the proteasome inhibitor Bortezomib. Apoptosis 2007 Jul; 12 (7): 1327-1338
102. Pitts TM, Morrow M, Kaufman SA, et al. Vorinostat and bortezomib exert synergistic antiproliferative and proapoptotic effects in colon cancer cell models. Mol Cancer Ther 2009 Feb; 8 (2): 342-349
103. Lin Z, Bazzaro M, Wang MC, et al. Combination of proteasome and HDAC inhibitors for uterine cervical cancer treatment. Clin Cancer Res 2009 Jan 15; 15 (2): 570-577
104. Nawrocki ST, Carew JS, Pino MS, et al. Aggresome disruption: a novel strategy to enhance bortezomib-induced apoptosis in pancreatic cancer cells. Cancer Res 2006 Apr 1; 66 (7): 3773-3781
105. Catley L, Weisberg E, Kiziltepe T, et al. Aggresome induction by proteasome inhibitor bortezomib and alphatubulin hyperacetylation by tubulin deacetylase (TDAC) inhibitor LBH589 are synergistic in myeloma cells. Blood 2006 Nov 15; 108 (10): 3441-3449
106. Nawrocki ST, Carew JS, Maclean KH, et al. Myc regulates aggresome formation, the induction of Noxa, and apoptosis in response to the combination of bortezomib and SAHA. Blood 2008 Oct 1; 112 (7): 2917-2926
107. Badros AZ, Philip S, Niesvizk R, et al. Phase I trial of vorinostat plus bortezomib (bort) in relapsed/refractory multiple myeloma (mm) patients (pts) [abstract no. 8548]. 2008 Annual Meeting Proceedings of the American Society of Clinical Oncology (ASCO); 2008 May 30-Jun 3; Chicago (IL)
108. Petrella A, D'Acunto CW, Rodriquez M, et al. Effects of FR235222, a novel HDAC inhibitor, in proliferation and apoptosis of human leukaemia cell lines: role of annexin A1. Eur J Cancer 2008 Mar; 44 (5): 740-749
109. Liu T, Kuljaca S, Tee A, et al. Histone deacetylase inhibitors: multifunctional anticancer agents. Cancer Treat Rev 2006 May; 32 (3): 157-165
110. Shabbeer S, Kortenhorst MS, Kachhap S, et al. Multiple Molecular pathways explain the anti-proliferative effect of valproic acid on prostate cancer cells in vitro and in vivo. Prostate 2007 Jul 1; 67 (10): 1099-1110
111. Jiang K, Sun J, Cheng J, et al. Akt mediates Ras downregulation of RhoB, a suppressor of transformation, invasion, and metastasis. Mol Cell Biol 2004 Jun; 24 (12): 5565-5576
112. Sawada K, Mitra AK, Radjabi AR, et al. Loss of Ecadherin promotes ovarian cancer metastasis via alpha 5-integrin, which is a therapeutic target. Cancer Res 2008 Apr 1; 68 (7): 2329-2339
113. Juan LJ, Shia WJ, Chen MH, et al. Histone deacetylases specifically down-regulate p53-dependent gene activation. J Biol Chem 2000 Jul 7; 275 (27): 20436-20443
114. Luo J, Su F, Chen D, et al. Deacetylation of p53 modulates its effect on cell growth and apoptosis. Nature 2000 Nov 16; 408 (6810): 377-381
115. Martinez-Balbas MA, Bauer UM, Nielsen SJ, et al. Regulation of E2F1 activity by acetylation. EMBO J 2000 Feb 15; 19 (4): 662-671
116. Kovacs JJ, Murphy PJ, Gaillard S, et al. HDAC6 regulates Hsp90 acetylation and chaperone-dependent activation of glucocorticoid receptor. Mol Cell 2005 May 27; 18 (5): 601-607
117. Jeong J, Juhn K, LeeH, et al. SIRT1 promotes DNA repair activity and deacetylation of Ku70. Exp Mol Med 2007 Feb 28; 39 (1): 8-13
118. Hubbert C, Guardiola A, Shao R, et al. HDAC6 is a microtubule-associated deacetylase. Nature 2002 May 23; 417 (6887): 455-458
119. Li Y, Zhang X, Polakiewicz RD, et al. HDAC6 is required for epidermal growth factor-induced beta-catenin nuclear localization. J Biol Chem 2008 May 9; 283 (19): 12686-12690
120. Ito A, Kawaguchi Y, Lai CH, et al. MDM2-HDAC1- mediated deacetylation of p53 is required for its degradation. EMBO J 2002 Nov 15; 21 (22): 6236-6245
121. Roy S, Tenniswood M. Site-specific acetylation of p53 directs selective transcription complex assembly. J Biol Chem 2007 Feb 16; 282 (7): 4765-4771
122. Lu Z, Luo RZ, Peng H, et al. E2F-HDAC complexes negatively regulate the tumor suppressor gene ARHI in breast cancer. Oncogene 2006 Jan 12; 25 (2): 230-239
123. Lu Z, Luo RZ, Peng H, et al. Transcriptional and posttranscriptional down-regulation of the imprinted tumor suppressor gene ARHI (DRAS3) in ovarian cancer. Clin Cancer Res 2006 Apr 15; 12 (8): 2404-2413
124. Feng W, Lu Z, Luo RZ, et al. Multiple histone deacetylases repress tumor suppressor gene ARHI in breast cancer. Int J Cancer 2007 Apr 15; 120 (8): 1664-1668
125. 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 2007 Jun 1; 67 (11): 5318-5327
126. Haggarty SJ, Koeller KM, Wong JC, et al. Domainselective small-molecule inhibitor of histone deacetylase 6 (HDAC6)-mediated tubulin deacetylation. Proc Natl Acad Sci U S A 2003 Apr 15; 100 (8): 4389-4394
127. Wang Y, Wang SY, Zhang XH, et al. FK228 inhibits Hsp90 chaperone function in K562 cells via hyperacetylation of Hsp70. Biochem Biophys Res Commun 2007 May 18; 356 (4): 998-1003
128. Sawada M, Sun W, Hayes P, et al. Ku70 suppresses the apoptotic translocation of Bax to mitochondria. Nat Cell Biol 2003 Apr; 5 (4): 320-329
129. Subramanian C, Opipari Jr AW, Bian X, et al. Ku70 acetylation mediates neuroblastoma cell death induced by histone deacetylase inhibitors. Proc Natl Acad Sci U S A 2005 Mar 29; 102 (13): 4842-4847
130. Shan B, Yao TP, Nguyen HT, et al. Requirement of HDAC6 for transforming growth factor-{beta}1-induced epithelial-mesenchymal transition. J Biol Chem 2008 Jul 25; 283 (30): 21065-21073
131. 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 2007 May 20; 25 (15): 1979-1985
132. 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 2007 Sep; 18 (9): 1529-1538
133. 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 2008 Oct 1; 14 (19): 6296-6301
134. 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 Jun 15; 13 (12): 3605-361
135. Pauer LR, Olivares J, Cunningham C, et al. Phase I study of oral CI-994 in combination with carboplatin and paclitaxel in the treatment of patients with advanced solid tumors. Cancer Invest 2004; 22 (6): 886-896
136. Sung MW, Waxman S. Combination of cytotoxicdifferentiation therapy with 5-fluorouracil and phenylbutyrate in patients with advanced colorectal cancer. Anticancer Res 2007 Mar-Apr; 27 (2): 995-1001
137. Undevia SD, Kindler HL, Janisch L, et al. A phase I study of the oral combination of CI-994, a putative histone deacetylase inhibitor, and capecitabine. Ann Oncol 2004 Nov; 15 (11): 1705-1711
138. Richards DA, Boehm KA, Waterhouse DM, et al. Gemcitabine plus CI-994 offers no advantage over gemcitabine alone in the treatment of patients with advanced pancreatic cancer: results of a phase II randomized, doubleblind, placebo-controlled, multicenter study. Ann Oncol 2006 Jul; 17 (7): 1096-1102
139. 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 Nov 1; 14 (21): 7138-7142
140. Woyach JA, Kloos RT, Ringel MD, et al. Lack of therapeutic effect of the histone deacetylase inhibitor vorinostat in patients with metastatic radioiodine-refractory thyroid carcinoma. J Clin Endocrinol Metab 2009 Jan; 94 (1): 164-170
141. Galanis E, Jaeckle KA, Maurer MJ, et al. Phase II trial of vorinostat in recurrent glioblastoma multiforme: a north central cancer treatment group study. J Clin Oncol 2009 Apr 20; 27 (12): 2052-2058
142. Ramalingam SS, Belani CP, Ruel C, et al. Phase II study of belinostat (PXD101), a histone deacetylase inhibitor, for second line therapy of advanced malignant pleural mesothelioma. J Thorac Oncol 2009 Jan; 4 (1): 97-101
143. Woo S, Gardner ER, Chen X, et al. Population pharmacokinetics of romidepsin in patients with cutaneous T-cell lymphoma and relapsed peripheral T-cell lymphoma. Clin Cancer Res 2009 Feb 15; 15 (4): 1496-1503
144. Kuendgen A, Knipp S, Fox F, et al. Results of a phase 2 study of valproic acid alone or in combination with alltrans retinoic acid in 75 patients with myelodysplastic syndrome and relapsed or refractory acute myeloid leukemia. Ann Hematol 2005 Dec; 84 Suppl. 1: 61-66
145. Gojo I, Jiemjit A, Trepel JB, et al. Phase 1 and pharmacologic study of MS-275, a histone deacetylase inhibitor, in adults with refractory and relapsed acute leukemias. Blood 2007 Apr 1; 109 (7): 2781-2790
146. Ryan QC, Headlee D, Acharya M, et al. Phase I and pharmacokinetic study of MS-275, a histone deacetylase inhibitor, in patients with advanced and refractory solid tumors or lymphoma. J Clin Oncol 2005 Jun 10; 23 (17): 3912-3922
147. Hauschild A, Trefzer U, Garbe C, et al. Multicenter phase II trial of the histone deacetylase inhibitor pyridylmethyl- N-{4-[(2-aminophenyl)-carbamoyl]- benzyl}-carbamate in pretreated metastatic melanoma. Melanoma Res 2008 Aug; 18 (4): 274-278
148. Marchion DC, Bicaku E, Turner JG, et al. Synergistic interaction between histone deacetylase and topoisomerase II inhibitors is mediated through topoisomerase IIbeta. Clin Cancer Res 2005 Dec 1; 11 (23): 8467-8475
149. Marchion DC, Bicaku E, Daud AI, et al. In vivo synergy between topoisomerase II and histone deacetylase inhibitors: predictive correlates. Mol Cancer Ther 2005 Dec; 4 (12): 1993-2000
150. Kaminskas E, Farrell AT, Wang YC, et al. FDA drug approval summary: azacitidine (5-azacytidine, Vidaza) for injectable suspension. Oncologist 2005 Mar; 10 (3): 176-182
151. 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 2006 Nov; 5 (11): 2767-2776
152. Catalano MG, Poli R, Pugliese M, et al. Valproic acid enhances tubulin acetylation and apoptotic activity of paclitaxel on anaplastic thyroid cancer cell lines. Endocr Relat Cancer 2007 Sep; 14 (3): 839-845
153. Lee JH, Park JH, Jung Y, et al. Histone deacetylase inhibitor enhances 5-fluorouracil cytotoxicity by downregulating thymidylate synthase in human cancer cells. Mol Cancer Ther 2006 Dec; 5 (12): 3085-3095
154. Gao N, Rahmani M, Shi X, et al. Synergistic antileukemic interactions between 2-medroxyestradiol (2-ME) and histone deacetylase inhibitors involve Akt down-regulation and oxidative stress. Blood 2006 Jan 1; 107 (1): 241-249
155. Zhao Y, Tan J, Zhuang L, et al. Inhibitors of histone deacetylases target the Rb-E2F1 pathway for apoptosis induction through activation of proapoptotic protein Bim. Proc Natl Acad Sci U S A 2005 Nov 1; 102 (44): 16090-16095
156. Cameron EE, Bachman KE, Myohanen S, et al. Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer. Nat Genet 1999 Jan; 21 (1): 103-107
157. Shiozawa K, Nakanishi T, TanM, et al. Preclinical studies of vorinostat (suberoylanilide hydroxamic acid) combined with cytosine arabinoside and etoposide for treatment of acute leukemias. Clin Cancer Res 2009 Mar 1; 15 (5): 1698-1707
158. Rubin EH, Agrawal NG, Friedman EJ, et al. A study to determine the effects of food and multiple dosing on the pharmacokinetics of vorinostat given orally to patients with advanced cancer. Clin Cancer Res 2006 Dec 1; 12 (23): 7039-7045