Developing histone deacetylase inhibitors in the therapeutic armamentarium of pancreatic adenocarcinoma

Expert Opinion on Therapeutic Targets

Volumn 16, Issue 7, 2012, Pages 707-718

  Zafar, Syed F ^a   Nagaraju, Ganji Purnachandra ^a   El Rayes, Bassel ^b  

^a EMORY UNIVERSITY   (United States)

^b EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

biology of histone deacetylase; drug development; epigenetic modulation; histone deacetylase inhibitors; pancreatic adenocarcinoma

Indexed keywords

5 AZA 2' DEOXYCYTIDINE; BELINOSTAT; DACINOSTAT; ENTINOSTAT; EPIDERMAL GROWTH FACTOR RECEPTOR; EPIRUBICIN; ETOPOSIDE; FR 235222; GARLIC EXTRACT; GEMCITABINE; GIVINOSTAT; HEAT SHOCK PROTEIN 90; HISTONE DEACETYLASE; HISTONE DEACETYLASE 1; HISTONE DEACETYLASE 2; HISTONE DEACETYLASE 3; HISTONE DEACETYLASE 6; HISTONE DEACETYLASE 7; HISTONE DEACETYLASE INHIBITOR; ISOFLAVONE; ISOTRETINOIN; PANOBINOSTAT; QUERCETIN; QUISINOSTAT; RESMINOSTAT; RESVERATROL; ROMIDEPSIN; SALINOSPORAMIDE A; SB 939; TACEDINALINE; TRICHOSTATIN A; UNCLASSIFIED DRUG; UNINDEXED DRUG; VALPROIC ACID; VORINOSTAT;

CARCINOGENESIS; CUTANEOUS T CELL LYMPHOMA; DRUG EFFECT; DRUG EFFICACY; DRUG MECHANISM; DRUG RESPONSE; ENZYME ACTIVITY; ENZYME INHIBITION; EPITHELIAL MESENCHYMAL TRANSITION; HUMAN; LUNG NON SMALL CELL CANCER; MELANOMA; PANCREAS ADENOCARCINOMA; PANCREAS CANCER; PROSTATE CANCER; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; PROTEIN TRANSPORT; REVIEW;

ADENOCARCINOMA; ANIMALS; ANTINEOPLASTIC AGENTS; EPITHELIAL-MESENCHYMAL TRANSITION; HISTONE DEACETYLASE INHIBITORS; HISTONE DEACETYLASES; HSP90 HEAT-SHOCK PROTEINS; HUMANS; NEOPLASTIC STEM CELLS; PANCREATIC NEOPLASMS; RECEPTOR, EPIDERMAL GROWTH FACTOR;

EID: 84862564949     PISSN: 14728222     EISSN: 17447631     Source Type: Journal    
DOI: 10.1517/14728222.2012.691473     Document Type: Review

References (121)

1. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin 2010;60(5):277-300
2. Kleeff J, Michalski CW, Friess H, Buchler MW. Surgical treatment of pancreatic cancer: the role of adjuvant and multimodal therapies. Eur J Surg Oncol 2007;33(7):817-23 (Pubitemid 47279053)
3. Minucci S, Pelicci PG. Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer. Nat Rev Cancer 2006;6(1):38-51 A very comprehensive review of epigenetic treatment of cancers and utilizing HDAC inhibitors. (Pubitemid 43054973)
4. Yang XJ, Seto E. Collaborative spirit of histone deacetylases in regulating chromatin structure and gene expression. Curr Opin Genet Dev 2003;13(2):143-53 (Pubitemid 36369738)
5. Jenuwein T, Allis CD. Translating the histone code. Science 2001;293(5532):1074-80 (Pubitemid 32758077)
6. Choudhary C, Kumar C, Gnad F, et al. Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science 2009;325(5942):834-40
7. Mann BS, Johnson JR, Cohen MH, et al. FDA approval summary: vorinostat for treatment of advanced primary cutaneous T-cell lymphoma. Oncologist 2007;12(10):1247-52 (Pubitemid 350106355)
8. Venugopal B, Evans TR. Developing histone deacetylase inhibitors as anti-cancer therapeutics. Curr Med Chem 2011;18(11):1658-71
9. Haberland M, Montgomery RL, Olson EN. The many roles of histone deacetylases in development and physiology: implications for disease and therapy. Nat Rev Genet 2009;10(1):32-42
10. Haigis MC, Guarente LP. Mammalian sirtuins - emerging roles in physiology, aging, and calorie restriction. Genes Dev 2006;20(21):2913-21 (Pubitemid 44771725)
11. Glozak MA, Seto E. Histone deacetylases and cancer. Oncogene 2007;26(37):5420-32 (Pubitemid 47255924)
12. Sengupta N, Seto E. Regulation of histone deacetylase activities. J Cell Biochem 2004;93(1):57-67
13. Lagger G, O'Carroll D, Rembold M, et al. Essential function of histone deacetylase 1 in proliferation control and CDK inhibitor repression. EMBO J 2002;21(11):2672-81 (Pubitemid 34619383)
14. Marchion DC, Bicaku E, Turner JG, et al. HDAC2 regulates chromatin plasticity and enhances DNA vulnerability. Mol Cancer Ther 2009;8(4):794-801
15. Bhaskara S, Chyla BJ, Amann JM, et al. Deletion of histone deacetylase 3 reveals critical roles in S phase progression and DNA damage control. Mol Cell 2008;30(1):61-72 (Pubitemid 351470157)
16. Mariadason JM. HDACs and HDAC inhibitors in colon cancer. Epigenetics 2008;3(1):28-37 (Pubitemid 351540961)
17. Dokmanovic M, Clarke C, Marks PA. Histone deacetylase inhibitors: overview and perspectives. Mol Cancer Res 2007;5(10):981-9 (Pubitemid 350080267)
18. Chang S, Young BD, Li S, et al. Histone deacetylase 7 maintains vascular integrity by repressing matrix metalloproteinase 10. Cell 2006;126(2):321-34 Important paper discussing the role of HDAC7 in repressing MMP10. (Pubitemid 44092958)
19. Zhang Y, Kwon S, Yamaguchi T, et al. Mice lacking histone deacetylase 6 have hyperacetylated tubulin but are viable and develop normally. Mol Cell Biol 2008;28(5):1688-701
20. Villagra A, Cheng F, Wang HW, et al. The histone deacetylase HDAC11 regulates the expression of interleukin 10 and immune tolerance. Nat Immunol 2009;10(1):92-100
21. Lane AA, Chabner BA. Histone deacetylase inhibitors in cancer therapy. J Clin Oncol 2009;27(32):5459-68
22. Zhang Y, Adachi M, Kawamura R, Imai K. Bmf is a possible mediator in histone deacetylase inhibitors FK228 and CBHA-induced apoptosis. Cell Death Differ 2006;13(1):129-40
23. 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 USA 2005;102(44):16090-5 Important paper discussing HDAC inhibition induces apoptosis via proapoptotic BH3-only protein Bim. (Pubitemid 41552872)
24. Ruefli AA, Ausserlechner MJ, Bernhard D, et al. The histone deacetylase inhibitor and chemotherapeutic agent suberoylanilide hydroxamic acid (SAHA) induces a cell-death pathway characterized by cleavage of Bid and production of reactive oxygen species. Proc Natl Acad Sci USA 2001;98(19):10833-8 (Pubitemid 32878706)
25. Prebet T, Vey N. Vorinostat in acute myeloid leukemia and myelodysplastic syndromes. Expert Opin Investig Drugs 2011;20(2):287-95
26. Insinga A, Monestiroli S, Ronzoni S, et al. Inhibitors of histone deacetylases induce tumor-selective apoptosis through activation of the death receptor pathway. Nat Med 2005;11(1):71-6 Important paper discussing that HDAC inhibition induced apoptosis is p53 independent involving the death receptor pathway. (Pubitemid 40215840)
27. Sade H, Sarin A. Reactive oxygen species regulate quiescent T-cell apoptosis via the BH3-only proapoptotic protein BIM. Cell Death Differ 2004;11(4):416-23 (Pubitemid 38489419)
28. Carew JS, Giles FJ, Nawrocki ST. Histone deacetylase inhibitors: mechanisms of cell death and promise in combination cancer therapy. Cancer Lett 2008;269(1):7-17
29. Kim MS, Kwon HJ, Lee YM, et al. Histone deacetylases induce angiogenesis by negative regulation of tumor suppressor genes. Nat Med 2001;7(4):437-43 (Pubitemid 32298546)
30. Ellis L, Hammers H, Pili R. Targeting tumor angiogenesis with histone deacetylase inhibitors. Cancer Lett 2009;280(2):145-53
31. Qian DZ, Kachhap SK, Collis SJ, et al. Class II histone deacetylases are associated with VHL-independent regulation of hypoxia-inducible factor 1 alpha. Cancer Res 2006;66(17):8814-21 (Pubitemid 44449199)
32. Deroanne CF, Bonjean K, Servotte S, et al. Histone deacetylases inhibitors as anti-angiogenic agents altering vascular endothelial growth factor signaling. Oncogene 2002;21(3):427-36 (Pubitemid 34123805)
33. Burgess AJ, Pavey S, Warrener R, et al. Up-regulation of p21(WAF1/CIP1) by histone deacetylase inhibitors reduces their cytotoxicity. Mol Pharmacol 2001;60(4):828-37 (Pubitemid 32900266)
34. Archer SY, Meng S, Shei A. Hodin RA. p21(WAF1) is required for butyrate-mediated growth inhibition of human colon cancer cells. Proc Natl Acad Sci USA 1998;95(12):6791-6
35. Huang BH, Laban M, Leung CH, et al. Inhibition of histone deacetylase 2 increases apoptosis and p21Cip1/WAF1 expression, independent of histone deacetylase 1. Cell Death Differ 2005;12(4):395-404 (Pubitemid 40520691)
36. Qiu L, Burgess A, Fairlie DP, et al. Histone deacetylase inhibitors trigger a G2 checkpoint in normal cells that is defective in tumor cells. Mol Biol Cell 2000;11(6):2069-83 (Pubitemid 30408065)
37. Nakagawa M, Oda Y, Eguchi T, et al. Expression profile of class I histone deacetylases in human cancer tissues. Oncol Rep 2007;18(4):769-74
38. Liu T, Kuljaca S, Tee A, Marshall GM. Histone deacetylase inhibitors: multifunctional anticancer agents. Cancer Treat Rev 2006;32(3):157-65
39. 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(3):e1-9 (Pubitemid 351440946)
40. Fritsche P, Seidler B, Schuler S, et al. HDAC2 mediates therapeutic resistance of pancreatic cancer cells via the BH3-only protein NOXA. Gut 2009;58(10):1399-409
41. Ouaissi M, Sielezneff I, Silvestre R, et al. High histone deacetylase 7 (HDAC7) expression is significantly associated with adenocarcinomas of the pancreas. Ann Surg Oncol 2008;15(8):2318-28
42. 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 2008;98(3):604-10 (Pubitemid 351214528)
43. Marks PA. The clinical development of histone deacetylase inhibitors as targeted anticancer drugs. Expert Opin Investig Drugs 2010;19(9):1049-66
44. Zhu P, Martin E, Mengwasser J, et al. Induction of HDAC2 expression upon loss of APC in colorectal tumorigenesis. Cancer Cell 2004;5(5):455-63 (Pubitemid 38610247)
45. Song J, Noh JH, Lee JH, et al. Increased expression of histone deacetylase 2 is found in human gastric cancer. APMIS 2005;113(4):264-8 (Pubitemid 40676807)
46. Wilson AJ, Byun DS, Popova N, et al. Histone deacetylase 3 (HDAC3) and other class I HDACs regulate colon cell maturation and p21 expression and are deregulated in human colon cancer. J Biol Chem 2006;281(19):13548-58 (Pubitemid 43855268)
47. Weichert W, Roske A, Niesporek S, et al. Class I histone deacetylase expression has independent prognostic impact in human colorectal cancer: specific role of class I histone deacetylases in vitro and in vivo. Clin Cancer Res 2008;14(6):1669-77 (Pubitemid 351469450)
48. Donadelli M, Costanzo C, Faggioli L, et al. Trichostatin A, an inhibitor of histone deacetylases, strongly suppresses growth of pancreatic adenocarcinoma cells. Mol Carcinog 2003;38(2):59-69 (Pubitemid 37255141)
49. Kumagai T, Wakimoto N, Yin D, et al. Histone deacetylase inhibitor, suberoylanilide hydroxamic acid (Vorinostat, SAHA) profoundly inhibits the growth of human pancreatic cancer cells. Int J Cancer 2007;121(3):656-65 (Pubitemid 46986501)
50. Sato N, Ohta T, Kitagawa H, et al. FR901228, a novel histone deacetylase inhibitor, induces cell cycle arrest and subsequent apoptosis in refractory human pancreatic cancer cells. Int J Oncol 2004;24(3):679-85
51. Sowa Y, Orita T, Minamikawa S, et al. Histone deacetylase inhibitor activates the WAF1/Cip1 gene promoter through the Sp1 sites. Biochem Biophys Res Commun 1997;241(1):142-50 (Pubitemid 28033553)
52. Moore PS, Barbi S, Donadelli M, et al. Gene expression profiling after treatment with the histone deacetylase inhibitor trichostatin A reveals altered expression of both proand anti-apoptotic genes in pancreatic adenocarcinoma cells. Biochim Biophys Acta 2004;1693(3):167-76 (Pubitemid 39198954)
53. Ryu JK, Lee WJ, Lee KH, et al. SK-7041, a new histone deacetylase inhibitor, induces G2-M cell cycle arrest and apoptosis in pancreatic cancer cell lines. Cancer Lett 2006;237(1):143-54
54. Arlt A, Gehrz A, Muerkoster S, et al. Role of NF-kappaB and Akt/PI3K in the resistance of pancreatic carcinoma cell lines against gemcitabine-induced cell death. Oncogene 2003;22(21):3243-51 (Pubitemid 36712936)
55. Karin M, Cao Y, Greten FR, Li ZW. NF-kappaB in cancer: from innocent bystander to major culprit. Nat Rev Cancer 2002;2(4):301-10 (Pubitemid 37328783)
56. Weichert W, Boehm M, Gekeler V, et al. High expression of RelA/p65 is associated with activation of nuclear factor-kappaB-dependent signaling in pancreatic cancer and marks a patient population with poor prognosis. Br J Cancer 2007;97(4):523-30 (Pubitemid 47258447)
57. Lehmann A, Denkert C, Budczies J, et al. High class I HDAC activity and expression are associated with RelA/p65 activation in pancreatic cancer in vitro and in vivo. BMC Cancer 2009;9:395
58. Piacentini P, Donadelli M, Costanzo C, et al. Trichostatin A enhances the response of chemotherapeutic agents in inhibiting pancreatic cancer cell proliferation. Virchows Arch 2006;448(6):797-804 (Pubitemid 43824437)
59. Arnold NB, Arkus N, Gunn J, Korc M. The histone deacetylase inhibitor suberoylanilide hydroxamic acid induces growth inhibition and enhances gemcitabine-induced cell death in pancreatic cancer. Clin Cancer Res 2007;13(1):18-26 (Pubitemid 46121848)
60. Millward M, Price T, Townsend A, et al. Phase 1 clinical trial of the novel proteasome inhibitor marizomib with the histone deacetylase inhibitor vorinostat in patients with melanoma, pancreatic and lung cancer based on in vitro assessments of the combination. Investig New Drugs 2011. [Epub ahead of print]
61. 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;14(20):6663-73
62. 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 patientswith solid tumours. Br J Cancer 2010;103(1):12-17
63. 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, double-blind, placebo-controlled, multicenter study. Ann Oncol 2006;17(7):1096-102 (Pubitemid 43985245)
64. 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;25(15):1979-85 (Pubitemid 46972780)
65. Pili R, Salumbides B, Zhao M, et al. Phase I study of the histone deacetylase inhibitor entinostat in combination with 13-cis retinoic acid in patients with solid tumours. Br J Cancer 2012;106(1):77-84
66. Altucci L, Gronemeyer H. The promise of retinoids to fight against cancer. Nat Rev Cancer 2001;1(3):181-93 (Pubitemid 33741893)
67. 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;113(18):4289-99
68. 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;66(7):3773-81 Important paper discussing aggresome disruption via HDAC inhibition and showing the utility of this novel approach in targeting PA cells.
69. Shankar S, Nall D, Tang SN, et al. Resveratrol inhibits pancreatic cancer stem cell characteristics in human and KrasG12D transgenic mice by inhibiting pluripotency maintaining factors and epithelial-mesenchymal transition. PLoS One 2011;6(1):e16530
70. Ansari D, Chen BC, Dong L, et al. Pancreatic cancer: translational research aspects and clinical implications. World J Gastroenterol 2012;18(13):1417-24
71. Nalls D, Tang SN, Rodova M, et al. Targeting epigenetic regulation of miR-34a for treatment of pancreatic cancer by inhibition of pancreatic cancer stem cells. PLoS One 2011;6(8):e24099
72. Volinia S, Calin GA, Liu CG, et al. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci USA 2006;103(7):2257-61 (Pubitemid 43271657)
73. Sharma SV, Lee DY, Li B, et al. A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations. Cell 2010;141(1):69-80 Important paper detailing the nature and character of drug tolerant subpopulation in cancer cells.
74. 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;44(5):740-9
75. Furumai R, Matsuyama A, Kobashi N, et al. FK228 (depsipeptide) as a natural prodrug that inhibits class I histone deacetylases. Cancer Res 2002;62(17):4916-21 (Pubitemid 34984414)
76. Kim DH, Shin J, Kwon HJ. Psammaplin A is a natural prodrug that inhibits class I histone deacetylase. Exp Mol Med 2007;39(1):47-55 (Pubitemid 46356005)
77. Nian H, Delage B, Pinto JT, Dashwood RH. Allyl mercaptan, a garlic-derived organosulfur compound, inhibits histone deacetylase and enhances Sp3 binding on the P21WAF1 promoter. Carcinogenesis 2008;29(9):1816-24
78. Druesne N, Pagniez A, Mayeur C, et al. Diallyl disulfide (DADS) increases histone acetylation and p21(waf1/cip1) expression in human colon tumor cell lines. Carcinogenesis 2004;25(7):1227-36 (Pubitemid 38968051)
79. Wang RH, Zheng Y, Kim HS, et al. Interplay among BRCA1, SIRT1, and Survivin during BRCA1-associated tumorigenesis. Mol Cell 2008;32(1):11-20
80. Link A, Balaguer F, Goel A. Cancer chemoprevention by dietary polyphenols: promising role for epigenetics. Biochem Pharmacol 2010;80(12):1771-92
81. Thiery JP, Sleeman JP. Complex networks orchestrate epithelial- mesenchymal transitions. Nat Rev Mol Cell Biol 2006;7(2):131-42 (Pubitemid 43278296)
82. Yang J, Weinberg RA. Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis. Dev Cell 2008;14(6):818-29 (Pubitemid 351757205)
83. Kalluri R, Weinberg RA. The basics of epithelial-mesenchymal transition. J Clin Invest 2009;119(6):1420-8
84. von Burstin J, Eser S, Paul MC, et al. E-cadherin regulates metastasis of pancreatic cancer in vivo and is suppressed by a SNAIL/HDAC1/HDAC2 repressor complex. Gastroenterology 2009;137(1):361-71; 71 e1-5
85. Schneider G, Kramer OH, Schmid RM, Saur D. Acetylation as a transcriptional control mechanism-HDACs and HATs in pancreatic ductal adenocarcinoma. J Gastrointest Cancer 2011;42(2):85-92
86. Massague J. TGFbeta in Cancer. Cell 2008;134(2):215-30
87. Shan B, Yao TP, Nguyen HT, et al. Requirement of HDAC6 for transforming growth factor-beta1-induced epithelial-mesenchymal transition. J Biol Chem 2008;283(30):21065-73
88. Roberts AB, Tian F, Byfield SD, et al. Smad3 is key to TGF-beta-mediated epithelial-to-mesenchymal transition, fibrosis, tumor suppression and metastasis. Cytokine Growth Factor Rev 2006;17(1-2):19-27 (Pubitemid 43117513)
89. Sarkar FH, Li Y, Wang Z, Kong D. Pancreatic cancer stem cells and EMT in drug resistance and metastasis. Minerva Chir 2009;64(5):489-500
90. Chun SG, Zhou W, Yee NS. Combined targeting of histone deacetylases and hedgehog signaling enhances cytoxicity in pancreatic cancer. Cancer Biol Ther 2009;8(14):1328-39
91. Parmigiani RB, Xu WS, Venta-Perez G, et al. HDAC6 is a specific deacetylase of peroxiredoxins and is involved in redox regulation. Proc Natl Acad Sci USA 2008;105(28):9633-8 (Pubitemid 352031352)
92. Haggarty SJ, Koeller KM, Wong JC, et al. Domain-selective small-molecule inhibitor of histone deacetylase 6 (HDAC6)-mediated tubulin deacetylation. Proc Natl Acad Sci USA 2003;100(8):4389-94 (Pubitemid 36457739)
93. Bali P, Pranpat M, Bradner J, et al. Inhibition of histone deacetylase 6 acetylates and disrupts the chaperone function of heat shock protein 90: a novel basis for antileukemia activity of histone deacetylase inhibitors. J Biol Chem 2005;280(29):26729-34 (Pubitemid 41040705)
94. Ogata M, Naito Z, Tanaka S, et al. Overexpression and localization of heatshock proteins mRNA in pancreatic carcinoma. J Nihon Med Sch 2000;67(3):177-85
95. Goetz MP, Toft DO, Ames MM, Erlichman C. The Hsp90 chaperone complex as a novel target for cancer therapy. Ann Oncol 2003;14(8):1169-76 (Pubitemid 37039035)
96. Whitesell L, Lindquist SL. HSP90 and the chaperoning of cancer. Nat Rev Cancer 2005;5(10):761-72 (Pubitemid 41400776)
97. Basso AD, Solit DB, Chiosis G, et al. Akt forms an intracellular complex with heat shock protein 90 (Hsp90) and Cdc37 and is destabilized by inhibitors of Hsp90 function. J Biol Chem 2002;277(42):39858-66 (Pubitemid 35190971)
98. Matthaios D, Zarogoulidis P, Balgouranidou I, et al. Molecular pathogenesis of pancreatic cancer and clinical perspectives. Oncology 2011;81(3-4):259-72
99. Lang SA, Moser C, Gaumann A, et al. Targeting heat shock protein 90 in pancreatic cancer impairs insulin-like growth factor-I receptor signaling, disrupts an interleukin-6/signaltransducer and activator of transcription 3/hypoxia-inducible factor-1alpha autocrine loop, and reduces orthotopic tumor growth. Clin Cancer Res 2007;13(21):6459-68 (Pubitemid 350075036)
100. Kovacs JJ, Murphy PJ, Gaillard S, et al. HDAC6 regulates Hsp90 acetylation and chaperone-dependent activation of glucocorticoid receptor. Mol Cell 2005;18(5):601-7 Important paper introducing the concept of HDAC6 regulation of of HSP90 acetylation. (Pubitemid 40726236)
101. Chiosis G, Vilenchik M, Kim J, Solit D. Hsp90: the vulnerable chaperone. Drug Discov Today 2004;9(20):881-8 (Pubitemid 39314553)
102. Li D, Marchenko ND, Moll UM. SAHA shows preferential cytotoxicity in mutant p53 cancer cells by destabilizing mutant p53 through inhibition of the HDAC6-Hsp90 chaperone axis. Cell Death Differ 2011;18(12):1904-13
103. Namdar M, Perez G, Ngo L, Marks PA. Selective inhibition of histone deacetylase 6 (HDAC6) induces DNA damage and sensitizes transformed cells to anticancer agents. Proc Natl Acad Sci USA 2010;107(46):20003-8
104. Kawaguchi Y, Kovacs JJ, McLaurin A, et al. The deacetylase HDAC6 regulates aggresome formation and cell viability in response to misfolded protein stress. Cell 2003;115(6):727-38 (Pubitemid 38030301)
105. Levine B. Eating oneself and uninvited guests: autophagy-related pathways in cellular defense. Cell 2005;120(2):159-62 (Pubitemid 40174758)
106. Mizushima N, Levine B, Cuervo AM, Klionsky DJ. Autophagy fights disease through cellular self-digestion. Nature 2008;451(7182):1069-75 (Pubitemid 351317450)
107. Lee JY, Koga H, Kawaguchi Y, et al. HDAC6 controls autophagosome maturation essential for ubiquitin-selective quality-control autophagy. EMBO J 2010;29(5):969-80
108. Rikiishi H. Autophagic and apoptotic effects of HDAC inhibitors on cancer cells. J Biomed Biotechnol 2011;2011:830260
109. Yang S, Wang X, Contino G, et al. Pancreatic cancers require autophagy for tumor growth. Genes Dev 2011;25(7):717-29
110. Mujumdar N, Saluja AK. Autophagy in pancreatic cancer: an emerging mechanism of cell death. Autophagy 2010;6(7):997-8
111. Pardo R, Lo Re A, Archange C, et al. Gemcitabine induces the VMP1-mediated autophagy pathway to promote apoptotic death in human pancreatic cancer cells. Pancreatology 2010;10(1):19-26
112. Wong HH, Lemoine NR. Pancreatic cancer: molecular pathogenesis and new therapeutic targets. Nat Rev Gastroenterol Hepatol 2009;6(7):412-22
113. Matsuda K, Idezawa T, You XJ, et al. Multiple mitogenic pathways in pancreatic cancer cells are blocked by a truncated epidermal growth factor receptor. Cancer Res 2002;62(19):5611-17
114. Deribe YL, Wild P, Chandrashaker A, et al. Regulation of epidermal growth factor receptor trafficking by lysine deacetylase HDAC6. Sci Signal 2009:2(102):ra84
115. Arts J, King P, Marien A, et al. JNJ-26481585, a novel "second-generation" oral histone deacetylase inhibitor, shows broad-spectrum preclinical antitumoral activity. Clin Cancer Res 2009;15(22):6841-51
116. Oki Y, Copeland A, Younes A. Clinical development of panobinostat in classical Hodgkin's lymphoma. Expert Rev Hematol 2011;4(3):245-52
117. Lin H, Geng X, Dang W, et al. Molecular mechanisms associated with the antidepressant effects of the class I histone deacetylase inhibitor MS-275 in the rat ventrolateral orbital cortex. Brain Res 2012. [Epub ahead of print]
118. Novotny-Diermayr V, Sangthongpitag K, Hu CY, et al. SB939, a novel potent and orally active histone deacetylase inhibitor with high tumor exposure and efficacy in mouse models of colorectal cancer. Mol Cancer Ther 2010;9(3):642-52
119. Plumb JA, Finn PW, Williams RJ, et al. Pharmacodynamic response and inhibition of growth of human tumor xenografts by the novel histone deacetylase inhibitor PXD101. Mol Cancer Ther 2003;2(8):721-8
120. Golay J, Cuppini L, Leoni F, et al. The histone deacetylase inhibitor ITF2357 has anti-leukemic activity in vitro and in vivo and inhibits IL-6 and VEGF production by stromal cells. Leukemia 2007;21(9):1892-900 (Pubitemid 47299961)
121. Mandl-Weber S, Meinel FG, Jankowsky R, et al. The novel inhibitor of histone deacetylase resminostat (RAS2410) inhibits proliferation and induces apoptosis in multiple myeloma (MM) cells. Br J Haematol 2010;149(4):518-28