Novel therapeutic strategies in multiple myeloma: Role of the heat shock protein inhibitors

European Journal of Haematology

Volumn 86, Issue 2, 2011, Pages 93-110

  Allegra, Alessandro ^a   Sant'Antonio, Emanuela ^a   Penna, Giuseppa ^a   Alonci, Andrea ^a   D'Angelo, Arianna ^a   Russo, Sabina ^a   Cannavò, Antonino ^a   Gerace, Demetrio ^a   Musolino, Caterina ^a  

^a UNIVERSITY OF MESSINA   (Italy)

Author keywords

Client protein; Heat shock protein; Multiple myeloma

Indexed keywords

5 (2,4 DIHYDROXY 5 ISOPROPYLPHENYL) 4 (4 MORPHOLINOMETHYLPHENYL) 3 ISOXAZOLECARBOXYLIC ACID ETHYLAMIDE; ALVESPIMYCIN; ANSAMYCIN DERIVATIVE; ANTINEOPLASTIC AGENT; BORTEZOMIB; CISPLATIN; DACTINOMYCIN; DOXORUBICIN; GELDANAMYCIN; GEMCITABINE; HEAT SHOCK PROTEIN 90; HEAT SHOCK PROTEIN 90 INHIBITOR; HISTONE DEACETYLASE INHIBITOR; IMATINIB; IRINOTECAN; KW 2478; MELPHALAN; NANOPARTICLE; NOVOBIOCIN; NVP BEP 800; PACLITAXEL; PANOBINOSTAT; PERIFOSINE; RADICICOL; RETASPIMYCIN; SNX 2112; SNX 5422; TANESPIMYCIN; UNCLASSIFIED DRUG; UNINDEXED DRUG; VORINOSTAT;

ABSENCE OF SIDE EFFECTS; ACUTE GRANULOCYTIC LEUKEMIA; ANGIOGENESIS; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; AUTOPHAGY; CANCER CELL CULTURE; CANCER RESEARCH; CARDIOTOXICITY; CHRONIC MYELOID LEUKEMIA; COLORECTAL CANCER; CYTOTOXICITY; DIARRHEA; DRUG DOSE ESCALATION; DRUG DOSE SEQUENCE; DRUG EFFICACY; DRUG POTENTIATION; DRUG SAFETY; DRUG SYNTHESIS; DRUG TARGETING; HEMATOLOGIC MALIGNANCY; HUMAN; IN VITRO STUDY; IN VIVO STUDY; LEUKEMIA; LEUKEMIA CELL; LIVER TOXICITY; LOW DRUG DOSE; LUNG CANCER; MULTIPLE CYCLE TREATMENT; MULTIPLE MYELOMA; MYELOMA CELL; NANOTECHNOLOGY; NAUSEA; NONHUMAN; ONCOLOGY; OVARY CANCER; PANCREAS CANCER; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROTEIN PROTEIN INTERACTION; RECOMMENDED DRUG DOSE; REVIEW; SOLID TUMOR; THROMBOCYTOPENIA; TREATMENT OUTCOME; VOMITING;

ANIMALS; ANTINEOPLASTIC AGENTS; AUTOPHAGY; CLINICAL TRIALS AS TOPIC; EPIGENESIS, GENETIC; HEAT-SHOCK PROTEINS; HSP90 HEAT-SHOCK PROTEINS; HUMANS; MEDICAL ONCOLOGY; MICE; MULTIPLE MYELOMA; NEOVASCULARIZATION, PATHOLOGIC;

EID: 78651423838     PISSN: 09024441     EISSN: 16000609     Source Type: Journal    
DOI: 10.1111/j.1600-0609.2010.01558.x     Document Type: Review

References (193)

1. Kyle RA, Gertz MA, Witzig TE, et al. Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc 2003;78:21-33.
2. Lonial S, Cavenagh J. Emerging combination treatment strategies containing novel agents in newly diagnosed multiple myeloma. Br J Haematol 2009;145:681-708.
3. Kastritis E, Zervas K, Symeonidis A, et al. Improved survival of patients with multiple myeloma after the introduction of novel agents and the applicability of the International Staging System (ISS): an analysis of the Greek Myeloma Study Group (GMSG). Leukemia 2009;23:1152-7.
4. Kumar SK, Rajkumar SV, Dispenzieri A, et al. Improved survival in multiple myeloma and the impact of novel therapies. Blood 2008;111:2516-20.
5. Anderson KC, Hannah AL, Pazdur R, Farrell AT. A strategic framework for novel drug development in multiple myeloma. Br J Haematol. 2007;138:153-9.
6. Mitsiades CS, Hideshima T, Chauhan D, McMillin DW, Klippel S, Laubach JP, Munshi NC, Anderson KC, Richardson PG. Emerging treatments for multiple myeloma: beyond immunomodulatory drugs and bortezomib. Semin Hematol 2009;46:166-75.
7. Hideshima T, Bergsagel PL, Kuehl WM, Anderson KC. Advances in biology of multiple myeloma: clinical applications. Blood 2004;104:607-18.
8. Mitsiades CS, Hayden PJ, Anderson KC, Richardson PG. From the bench to the bedside: emerging new treatments in multiple myeloma. Baillieres Best Pract Res Clin Haematol 2007;20:797-816.
9. Podar K, Chauhan D, Anderson KC. Bone marrow microenvironment and the identification of new targets for myeloma therapy. Leukemia 2009;23:10-24.
10. Isaacs JS, Xu W, Neckers L. Heat shock protein 90 as a molecular target for cancer therapeutics. Cancer Cell 2003;3:213-7.
11. Mahindra A, Cirstea D, Raje N. Novel therapeutic targets for multiple myeloma. Future Oncol 2010;6:407-18.
12. Takayama S, Reed JC, Homma S. Heat-shock proteins as regulators of apoptosis. Oncogene, 2003;22:9041-7.
13. Whitesell L, Lindquist SL. HSP90 and the chaperoning of cancer. Nat Rev Cancer 2005;5:761-72.
14. Cerchietti LC, Lopews EC, Yang SN, et al. Heat shock inhibitors kill diffuse large cell lymphoma destabilizing BCL-6 and have specific antitumor activity. Nat Med 2009;15:1369-76.
15. Sharma A, Meena AS, Bhat MK. Hyperthermia-associated carboplatin resistance: differential role of p53, HSF1 and HSP70 in hepatoma cells. Cancer Sci 2010;101:1186-93.
16. Kim YS, Alarcon SV, Lee S, Lee MJ, Giaccone G, Neckers L, Trepel JB. Update on HSP90 Inhibitors in Clinical Trial. Curr Top Med Chem 2009;9:1479-92.
17. Wong C, Chen S. Heat shock protein 90 inhibitors: new mode of therapy to overcome endocrine resistance. Cancer Res 2009;69:8670-7.
18. Richardson P, Chanan-Khan AA, Lonial S, et al. A multicenter phase 1 clinical trial of Tanespimycin (KOS-953) + Bortezomib (BZ): encouraging activity and manageable toxicity in heavily pre-treated patients with relapsed refractory multiple myeloma (MM). ASH Annual Meeting Abs 2006;108:406 (abstract).
19. Ritossa F. A new puffing pattern induced and temperature shock and DNP in Drosophila. Experientia 1962;18:571-3.
20. Ritossa F. Discovery of the heat shock response. Cell Stress Chaperones 1996;1:97-8.
21. Leppa S, Sistonen L. Heat shock response-pathophysiological implications. Ann Intern Med 1997;29:73-8.
22. Jolly C, Morimoto RI. Role of the heat shock response and molecular chaperones in oncogenesis and cell death. J Natl Cancer Inst 2000;92:1564-72.
23. Wegele H, Muller L, Buchner J. HSP70 and HSP90 - a relay team for protein folding. Rev Physiol Biochem Pharmacol 2004;151:1-44.
24. Hickey E, Brandon SE, Smale G, Lloyd D, Weber LA. Sequence and regulation of a gene encoding a human 89-kilodalton heat shock protein. Mol Cell Biol 1989;9:2615-26.
25. Csermely P, Schnaider T, Soti C, Prohaskka Z, Nardai G. The 90-kDa molecular chaperone family: structure, function, and clinical applications. A comprehensive review. Pharmacol Ther 1998;79:129-68.
26. Prodromou C, Roe SM, O'Brien R, Ladbury JE, Piper PW, Pearl LH. Identification and structural characterization of the ATP/ADP binding site in the HSP90 molecular chaperone. Cell 1997;90:65-75.
27. Gress TM, Müller-Pillasch F, Weber C, Lerch MM, Friess H, Büchler M, Beger HG, Adler G. Differential expression of heat shock proteins in pancreatic carcinoma. Cancer Res 1994;54:547-51.
28. Torronteguy C, Frasson A, Zerwes F, Winnikov E, da Silva VD, Ménoret A, Bonorino C. Inducible heat shock protein 70 expression as a potential predictive marker of metastasis in breast tumors. Cell Stress Chaperones 2006;11:34-43.
29. Kaur J, Ralhan R. Differential expression of 70-kDa heat shock-protein in human oral tumorigenesis. Int J Cancer 1995;63:774-9.
30. Chant ID, Rose PE, Morris AG. Analysis of heat shock protein expression in myeloid leukaemia cells by flow cytometry. Br J Haematol 1995;90:163-8.
31. Guo F, Sigua C, Bali P, et al. Mechanistic role of heat shock protein 70 in Bcr-Abl-mediated resistance to apoptosis in human acute leukemia cells. Blood 2005;105:1246-55.
32. Flandrin P, Guyotat D, Duval A, Cornillon J, Tavernier E, Nadal N, Campos L. Significance of heat-shock protein (HSP) 90 expression in acute myeloid leukemia cells. Cell Stress Chaperones 2008;13:357-64.
33. Fuqua SA, Oesterreich S, Hilsenbeck SG, Von Hoff DD, Eckardt J, Osborne CK. Heat shock proteins and drug resistance. Breast Cancer Res Treat 1994;32:67-71.
34. Vargas-Roig LM, Gago FE, Tello O, Aznar JC, Ciocca DR. Heat shock protein expression and drug resistance in breast cancer patients treated with induction chemotherapy. Int J Cancer 1998;79:468-75.
35. Hartl FU, Hayer-Hartl M. Molecular chaperones in the cytosol: from nascent chain to folded protein. Science 2002;295:1852-8.
36. Freeman BC, Yamamoto KR. Disassembly of transcriptional regulatory complexes by molecular chaperones. Science 2002;296:2232-5.
37. Parmiani G, Testori A, Maio M, et al. Heat shock proteins and their use as anticancer vaccines. Clin Cancer Res 2004;10:8142-6.
38. Mosser DD, Caron AW, Bourget L, Denis-Larose C, Massie B. Role of the human heat shock protein HSP70 in protection against stress-induced apoptosis. Mol Cell Biol 1997;17:5317-27.
39. Van den Berghe T, Kalai M, van Loo G, Declercq W, Vandenabeele P. Disruption of HSP90 function reverts tumor necrosis factor-induced necrosis to apoptosis. J Biol Chem 2003;278:5622-9.
40. Chen G, Cao P, Goeddel DV. TNF-induced recruitment and activation of the IkK complex require Cdc37 and HSP90. Mol Cell 2002;9:401-10.
41. Falsone FM, Leptihn S, Osterauer A, Haslbeck M, Buchner J. Oncogenic mutations reduce the stability of Src kinase. J Mol Biol 2004;344:281-91.
42. Whitesell L, Sutphin PD, Pulcini EJ, Martinez JD, Cook PH. The physical association of multiple molecular chaperone proteins with mutant p53 is altered by geldanamycin, an HSP90-binding agent. Mol Cell Biol 1998;18:1517-24.
43. Whitesell L, Mimnaugh EG, De Costa B, Myers CE, Neckers LM. Inhibition of heat shock protein HSP90-pp60v-src heteroprotein complex formation by benzoquinone ansamycins: essential role for stress proteins in oncogenic transformation. Proc Natl Acad Sci USA 1994;91:8324-8.
44. Pandey P, Saleh A, Nakazawa A, et al. Negative regulation of cytochrome c-mediated oligomerization of APAF-1 and activation of procaspase-9 by heat shock protein 90. EMBO J 2000;19:4310-22.
45. Cohen-Saidon C, Carmi I, Keren A, Razin E. Antiaapoptotic function of Bcl-2 in mast cells is dependent on its association with heat shock protein 90beta. Blood 2006;107:1413-20.
46. Morimoto RI. Regulation of the heat shock transcriptional response: cross talk between a family of heat shock factors, molecular chaperones, and negative regulators. Genes Dev 1998;12:3788-96.
47. Sreedhar AS, Kalmár E, Csermely P, Shen YF. HSP90 isoforms: functions, expression and clinical importance. FEBS Lett 2004;562:11-5.
48. Richter K, Reinstein J, Buchner J. A Grp on the HSP90 mechanism. Mol Cell 2007;28:177-9.
49. Chen B, Piel WH, Gui L, Bruford E, Monteiro A. The HSP90 family of genes in the human genome: insights into their divergence and evolution. Genomics 2005;86:627-37.
50. Pratt WB, Toft DO. Steroid receptor interactions with heat shock protein and immunophilin chaperones. Endocr Rev 1997;18:306-60.
51. Xu W, Mimnaugh EG, Kim JS, Trepel JB, Neckers LM. HSP90, not Grp94, regulates the intracellular trafficking and stability of nascent ErbB2. Cell Stress Chaperones 2002;7:91-6.
52. Shiotsu Y, Soga S, Akinaga S. Heat shock protein 90-antagonist destabilizes Bcr-Abl/HSP90 chaperone complex. Leuk Lymphoma 2002;43:961-8.
53. Goetz MP, Toft DO, Ames MM, Erlichman C. The HSP90 chaperone complex as a novel target for cancer therapy. Ann Oncol 2003;14:1169-76.
54. Xu W, Neckers L. Targeting the molecular chaperone heat shock protein 90 provides a multifaceted effect on diverse cell signaling pathways of cancer cells. Clin Cancer Res 2007;13:1625-9.
55. Meyer P, Prodromou C, Hu B, Vaughan C, Roe SM, Panaretou B, Piper PW, Pearl LH. Structural and functional analysis of the middle segment of HSP90: implications for ATP hydrolysis and client protein and cochaperone interactions. Mol Cell 2003;11:647-58.
56. Pearl LH, Prodromou C. Structure, function, and mechanism of the HSP90 molecular chaperone. Adv Protein Chem 2001;59:157-86.
57. McLaughlin SH, Ventouras LA, Lobbezoo B, Jackson SE. Independent ATPase activity of HSP90 subunits creates a flexible assembly platform. J Mol Biol 2004;344:813-26.
58. Scheufler C, Brinker A, Bourenkov G, Pegoraro S, Moroder L, Bartunik H, Hartl FU, Moarefi I. Structure of TPR domain-peptide complexes: critical elements in the assembly of the HSP70-HSP90 multichaperone machine. Cell 2000;101:199-210.
59. Pearl LH. HSP90 and Cdc37 - a chaperone cancer conspiracy. Curr Opin Genet Dev 2005;15:55-61.
60. Smith JR, Clarke PA, de Billy E, Workman P. Silencing the cochaperone CDC37 destabilizes kinase clients and sensitizes cancer cells to HSP90 inhibitors. Oncogene 2009;28:157-69.
61. Smith JR, Workman P. Targeting CDC37: an alternative, kinase-directed strategy for disruption of oncogenic chaperoning. Cell Cycle 2009;8:362-72.
62. Uehara Y, Hori M, Takeuchi T, Umezawa H. Phenotypic change from transformed to normal induced by benzoquinonoid ansamycins accompanies inactivation of p60src in rat kidney cells infected with Rous sarcoma virus. Mol Cell Biol 1986;6:2198-206.
63. Deboer C, Meulman PA, Wnuk RJ, Peterson DH. Geldanamycin, a new antibiotic. J Antibiot 1970;23:442-7.
64. Whitesell L, Shifrin SD, Schwab G, Neckers LM. Benzoquinonoid ansamycins possess selective tumoricidal activity unrelated to src kinase inhibition. Cancer Res 1992;52:1721-8.
65. Banerji U, Judson I, Workman P. The clinical applications of heat shock protein inhibitors in cancer - present and future. Curr Cancer Drug Targets 2003;3:385-90.
66. Stebbins CE, Russo AA, Schneider C, Rosen N, Hartl FU, Pavletich NP. Crystal structure of an HSP90-geldanamycin complex: targeting of a protein chaperone by an antitumor agent. Cell 1997;89:239-50.
67. Panaretou B, Prodromou C, Roe SM, O'Brien R, Ladbury JE, Piper PW, Pearl LH. ATP binding and hydrolysis are essential to the function of HSP90 molecular chaperone in vivo. EMBO J 1998;17:4829-36.
68. Webb CP, Hose CD, Koochekpour S, Jeffers M, Oskarsson M, Sausville E, Monks A, Vande G, Woude GF. The geldanamycins are potent inhibitors of the hepatocyte growth factor/scatter factor-met-urokinase plasminogen activator-plasmin proteolytic network. Cancer Res 2000;60:342-9.
69. Supko JG, Hickman RL, Grever MR, Malspeis L. Preclinical pharmacologic evaluation of geldanamycin as an antitumour agent. Cancer Chemother Pharmacol 1995;36:305-15.
70. Egorin MJ, Rosen DM, Wolff JH, Callery PS, Musser SM, Eiseman JL. Metabolism of 17-(allyllamino)-17-demethoxygeldanamycin (NSC330507) by murine ad human hepatic preparations. Cancer Res 1998;58:2385-96.
71. Munster PN, Srethapakdi M, Moasser MM, Rosen N. Inhibition of heat shock protein 90 function by ansamycins causes the morphological and functional differentiation of breast cancer cells. Cancer Res 2001;61:2945-52.
72. Srethapakdi M, Liu F, Tavorath R, Rosen N. Inhibition of HSP90 function by ansamycins causes retinoblastoma gene product-dependent G1 arrest. Cancer Res 2000;60:3940-6.
73. Goes FS, Martin J. HSP90 chaperone complexes are required for the activity and stability of yeast protein kinases Mik1, Wee1 and Swe1. Eur J Biochem 2001;268:2281-9.
74. Kelland LR, Sharp SY, Rogers PM, Myers TG, Workman P. DT-Diaphorase expression and tumor cell sensitivity to 17-allylamino, 17-demethoxygeldanamycin, an inhibitor of heat shock protein 90. J Natl Cancer Inst 1999;91:1940-9.
75. Nimmanapalli R, O'Bryan E, Bhalla K. Geldanamycin and its analogue 17-allylamino-17-demethoxygeldanamycin lowers Bcr-Abl levels and induces apoptosis and differentiation of Bcr-Abl-positive human leukemic blasts. Cancer Res 2001;61:1799-804.
76. Glaze ER, Lambert AL, Smith AC, et al. Preclinical toxicity of a geldanamycin analog, 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG), in rats and dogs: Potential clinical relevance. Cancer Chemother Pharmacol 2005;56:637-47.
77. Waza M, Adachi H, Katsuno M, Minamiyama M, Tanaka F, Sobue G. Alleviating neurodegeneration by an anticancer agent: an HSP90 inhibitor (17-AAG). Ann N Y Acad Sci 2006;1086:21-34.
78. Adachi H, Waza M, Katsuno M, Tanaka F, Doyu M, Sobue G. Pathogenesis and molecular targeted therapy of spinal and bulbar muscular atrophy. Neuropathol Appl Neurobiol 2007;33:135-51.
79. Patterson J, Palombella VJ, Fritz C, Normant E. IPI-504, a novel and soluble HSP90 inhibitor, blocks the unfolded protein response in multiple myeloma cells. Cancer Chemother Pharmacol 2008;61:923-32.
80. Sydor JR, Normant E, Pien CS, et al. Development of 17-allylamino-17- demethoxygeldanamycin hydroquinone hydrochloride (IPI-504), an anti-cancer agent directed against HSP90. Proc Natl Acad Sci USA 2006;103:17408-13.
81. Banerji U, O'Donnell A, Scurr M. A pharmacokinetically (PK)-pharmacodynamically (PD) driven phase I trial of the HSP90 molecular chaperone inhibitor 17-allyamino 17-demethoxygeldanamycin (17AAG). Proc Am Assoc Cancer Res 2002;43:272.
82. Goetz MP, Toft D, Reid J, et al. Phase I trial of 17-allylamino-17-demethoxygeldanamycin in patients with advanced cancer. J Clin Oncol 2005;23:1078-87.
83. Grem JL, Morrison G, Guo XD, et al. Phase I and pharmacologic study of 17-(allylamino)-17-demethoxygeldanamycin in adult patients with solid tumors. J Clin Oncol 2005;23:1885-93.
84. Ramanathan RK, Egorin MJ, Eiseman JL, et al. Phase I and pharmacodynamic study of 17-(allylamino)-17-demethoxygeldanamycin in adult patients with refractory advanced cancers. Clin Cancer Res 2007;13:1769-74.
85. Solit DB, Ivy SP, Kopil C, et al. Phase I trial of 17-allylamino-17-demethoxygeldanamycin in patients with advanced cancer. Clin Cancer Res 2007;13:1775-82.
86. Nguyen DM, Chen A, Mixon A, Schrump DS. Sequence-dependent enhancement of paclitaxel toxicity in non-small cell lung cancer by 17-allylamino 17-demethoxygeldanamycin. J Thorac Cardiovasc Surg 1999;118:908-15.
87. Vasilevskaya IA, Rakitina TV, O'Dwyer PJ. Geldanamycin and its 17-allylamino-17-demethoxy analogue antagonize the action of Cisplatin in human colon adenocarcinoma cells: differential caspase activation as a basis for interaction. Cancer Res 2003;63:3241-6.
88. Tse A, Klimstra D, Gonen M, et al. A phase I dose-escalation study of irinotecan in combination with 17-Allylamino-17-demethoxygeldanamycib in patients with solid tumors. Clin Cancer Res 2008;14:6704-11.
89. Ramalingam S, Egorin M, Ramanathan R, et al. A phase I study of 17-Allylamino-17-Demethoxygeldanamycin combined with paclitaxel in patients with advanced solid malignancies. Clin Cancer Res 2008;14:345634-61.
90. George P, Bali P, Annavarapu S, et al. Combination of the histone deacetylase inhibitor LBH589 and the HSP90 inhibitor 17-AAG is highly active against human CML-BC cells and AML cells with activating mutation of FLT-3. Blood 2005;105:1768-76.
91. Nguyen TK, Rahmani M, Gao N, Kramer L, Corbin AS, Druker BJ, Dent P, Grant S. Synergistic interactions between DMAG and mitogen-activated protein kinase kinase 1/2 inhibitors in Bcr/abl+ leukemia cells sensitive and resistant to imatinib mesylate. Clin Cancer Res 2006;12:2239-47.
92. Radujkovic A, Schad M, Topaly J, Veldwijk MR, Laufs S, Schultheis BS, Jauch A, Melo JV, Fruehauf S, Zeller WJ. Synergistic activity of imatinib and 17-AAG in imatinib-resistant CML cells overexpressing BCR-ABL - Inhibition of P-glycoprotein function by 17-AAG. Leukemia 2005;19:1198-206.
93. Hubbard J, Erlichman C, Toft DO, Qin R, Stensgard BA, Felten S, Ten Eyck C, Batzel G, Ivy SP, Haluska P. Phase I study of 17-allylamino-17 demethoxygeldanamycin, gemcitabine and/or cisplatin in patients with refractory solid tumors. Invest New Drugs 2010;Jan 15 (Epub ahead of print)
94. Ge J, Normant E, Porter JR, et al. Design, synthesis, and biological evaluation of hydroquinone derivatives of 17-amino-17-demethoxygeldanamycin as potent, water-soluble inhibitors of HSP90. J Med Chem 2006;49:4606-16.
95. Peng C, Brain J, Hu Y, Goodrich A, Kong L, Grayzel D, Pak R, Read M, Li S. Inhibition of heat shock protein 90 prolongs survival of mice with BCR-ABL-T315I-induced leukemia and suppresses leukemic stem cells. Blood 2007;110:678-85.
96. Schulte TW, Akinaga S, Soga S, Sullivan W, Stensgard B, Toft D, Neckers LM. Antibiotic radicicol binds to the N terminal domain of HSP90 and shares important biologic activities with geldanamycin. Cell Stress Chaperones 1998;3:100-8.
97. Marcu MG, Schulte TW, Neckers L. Novobiocin and related coumarins and depletion of heat shock protein 90-dependent signaling proteins. J Natl Cancer Inst 2000;92:242-8.
98. Yu XM, Shen G, Neckers L, Blake H, Holzbeierlein J, Cronk B, Blagg BS. HSP90 inhibitors identified from a library of novobiocin analogues. J Am Chem Soc 2005;127:12778-9.
99. Burlison JA, Avila C, Vielhauer G, Lubbers DJ, Holzbeierlein J, Blagg BS. Development of novobiocin analogues that manifest anti-proliferative activity against several cancer cell lines. J Org Chem 2008;73:2130-7.
100. Holbeierlein JM, Windsperger A, Vielhauer G. HSP90: a drug target? Curr Oncol Rep 2010;12:95-101.
101. Lancet JBM, Gojo I, Burton M. Phase I, pharmacokinetic (PK) and pharmacodynamic (PD) study of intravenous alvespimycin (KOS-1022) in patients with refractory hematological malignancies. Blood 2006;108:1961 (abstract).
102. Steed P, Huang H, Fadden P. SNX-2112: a novel, selective, potent small molecule inhibitor of HSP90 with unique phamacodynamic properties. Eur J Cancer 2006;4:165 (abstract).
103. Hall SE, Barabasz A, Barta T. Chemoproteomics-driven drug discovery: identification of novel HSP90 inhibitors. AACR Annual Meeting; April 14-17, 2007; Los Angeles, CA. p. 4177.
104. Chandarlapaty S, Sawai A, Ye Q, et al. SNX-2112, a synthetic heat shock protein 90 inhibitor, has potent antitumor activity against HER kinase dependent cancers. Clin Cancer Res 2008;14:240-8.
105. Palermo CM, Westlake CA, Gasiewicz TA. Epigallocatechin gallate inhibits aryl hydrocarbon receptor gene transcription through an indirect mechanism involving binding to a 90 kDa heat shock protein. Biochemistry 2005;44:5041-52.
106. Baotran PL, Kim SA, Choi HS, Yoon JH, Ahn SG. Epigallocatechin-3-gallate suppresses the epression of HSP70 and HSP90 and exhibits anti-tumor activity in vitro and in vivo. BMC Cancer 2010;10:276.
107. Lancet JE, Gojo I, Barton M, et al. Phase I study of the heat shock protein 90 inhibitor alvespimycin (KOS-1022, 17DMAG) administered intravenously twice weekly bto patients with acute myeloid leukemia. Leukemia 2010;24:699-705.
108. Banerji U. Heat shock protein 90 as a drug target: some like it hot. Clin Cancer Res 2009;15:9-14.
109. Stephanou A, Conroy S, Isenberg DA, Maione D, Poli V, Ciliberto G, Latchman DS. Elevation of IL-6 in transgenic mice results in increased levels of the 90 kDa heat shock protein (HSP90) and the production of anti-HSP90 antibodies. J Autoimmun 1998;11:249-53.
110. Stephanou A, Amin V, Isenberg DA, Akira S, Kishimoto T, Latchman DS. Interleukin 6 activates heat-shock protein 90 beta gene expression. Biochem J 1997;321:1103-6.
111. Stephanou A, Isenberg DA, Akira S, Kishimoto T, Latchman DS. The nuclear factor interleukin-6 (NF-IL6) and signal transducer and activator of transcription-3 (STAT-3) signalling pathways co-operate to mediate the activation of the HSP90beta gene by interleukin-6 but have opposite effects on its inducibility by heat shock. Biochem J 1998;330:1189-95.
112. Kalvakolanu DV, Roy SK. CCAAT/enhancer binding proteins and interferon signaling pathways. J Interferon Cytokine Res 2005;25:757-69.
113. Andrulis M, Chatterjee M, Jain S, et al. Heat shock protein 90 alpha und beta are overexpressed in multiple myeloma cells and critically contribute to survival. Verh Dtsch Ges Pathol 2009;91:330-7.
114. Mitsiades CS, Mitsiades NS, McMullan CJ, et al. Antimyeloma activity of heat shock protein-90 inhibition. Blood 2006;107:1092-10100.
115. Giménez Ortiz A, Montalar Salcedo J. Heat shock proteins as targets in oncology. Clin Transl Oncol 2010;12:166-73.
116. Duus J, Bahar HI, Venkataraman G, Ozpuyan F, Izban KF, Al-Masri H, Maududi T, Toor A, Alkan S. Analysis of expression of heat shock protein-90 (HSP90) and the effects of HSP90 inhibitor (17-AAG) in multiple myeloma. Leuk Lymphoma 2006;47:1369-78.
117. Usmani SZ, Bona R, Li Z. 17 AAG for HSP90 inhibition in cancer- from bench to bedside. Curr Mol Med 2009;9:654-64.
118. Ramanathan RK, Trump DL, Eiseman JL, et al. Phase I pharmacokinetic-pharmacodynamic study of 17-(allylamino)-17-demethoxygeldanamycin (17AAG, NSC 330507), a novel inhibitor of heat shock protein 90, in patients with refractory advanced cancers. Clin Cancer Res 2005;11:3385-91.
119. Richardson PG, Chanan-Khan A, Lonial S. Tanespimycin + bortezomib in multiple myeloma: confirmation of the recommended dose using a novel formulation. Abst 1165 Am Soc Hematol annual Meeting, Atlanta, GA, December 9-11, 2007.
120. Mimnaugh EG, Xu W, Vos M, Yuan X, Isaacs JS, Bisht KS, Gius D, Neckers L. Simultaneous inhibition of HSP 90 and the proteasome promotes protein ubiquitination, causes endoplasmic reticulum-derived cytosolic vacuolization, and enhances antitumor activity. Mol Cancer Ther 2004;3:551-66.
121. Lanie K, Alsayed FY, Leleu X, et al. Combination MammalianTarget of Rapamycin Inhibitor Rapamycin and HSP90 Inhibitor 17-Allylamino-17-Demethoxygeldanamycin Has Synergistic Activity in Multiple Myeloma. Clin Cancer Res 2006;12:6826-35.
122. Cervantes-Gomez F, Nimmanapalli R, Gandhi V. Transcription inhibition of heat shock proteins: a strategy for combination of 17-allylamino-17-demethoxygeldanamycin and actinomycin D. Cancer Res 2009;1:3947-54.
123. Francis LK, Alsayed Y, Leleu X, et al. Combination mammalian target of rapamycin inhibitor rapamycin and HSP90 inhibitor 17-allylamino-17-demethoxygeldanamycin has synergistic activity in multiple myeloma. Clin Cancer Res 2006;12:6826-35.
124. Gupta D, Hideshima T, Anderson KC. Novel biologically based therapeutic strategies in myeloma. Revue in Clinical and Experimental Hematology 2002;6:301-24.
125. Huston A, Leleu X, Jia X, et al. Targeting Akt and Heat Shock Protein 90 Produces Synergistic Multiple Myeloma Cell Cytotoxicity in the Bone Marrow Microenvironment. Clin Cancer Res 2008;14:865-74.
126. Stühmer T, Zöllinger A, Siegmund D, et al. Signalling profile and antitumour activity of the novel HSP90 inhibitor NVP-AUY922 in multiple myeloma. Leukemia 2008;22:1604-12.
127. Kaiser M, Lamottke B, Mieth M, et al. Synergistic action of the novel HSP90 inhibitor NVP-AUY922 with histone deacetylase inhibitors, melphalan, or doxorubicin in multiple myeloma. Eur J Haematol 2010;84:337-44.
128. Stühmer T, Chatterjee M, Grella E, et al. Anti-myeloma activity of the novel 2-aminothienopyrimidine HSP90 inhibitor NVP-BEP800. Br J Haematol. 2009;147:319-27.
129. Okawa Y, Hideshima T, Steed P, et al. SNX-2112, a selective HSP90 inhibitor, potently inhibits tumor cell growth, angiogenesis, and osteoclastogenesis in multiple myeloma and other hematologic tumors by abrogating signaling via Akt and ERK. Blood 2009;113:846-55.
130. Nakashima T, Ishii T, Tagaya H, Seike T, Nakagawa H, Kanda Y, Akinaga S, Soga S, Shiotsu Y. New molecular and biological mechanism of antitumor activities of KW-2478, a novel nonansamycin heat shock protein 90 inhibitor, in multiple myeloma cells. Clin Cancer Res 2010;16:2792-802.
131. Obeng EA, Carlson LM, Gutman DM, Harrington WJ Jr, Lee KP, Boise LH. Proteasome inhibitors induce a terminal unfolded protein response in multiple myeloma cells. Blood 2006;107:4907-16.
132. Yasui H, Hideshima T, Ikeda H, et al. BIRB 796 enhances cytotoxicity triggered by bortezomib, heat shock protein (HSP) 90 inhibitor, and dexamethasone via inhibition of p38 mitogen-activated protein kinase/HSP27 pathway in multiple myeloma cell lines and inhibits paracrine tumour growth. Br J Haematol 2007;136:414-23.
133. Chauhan D, Singh A, Brahmandam M, Podar K, Hideshima T, Richardson P, Munshi N, Palladino MA, Anderson KC. Combination of proteasome inhibitors bortezomib and NPI-0052 trigger in vivo synergistic cytotoxicity in multiple myeloma. Blood 2008;111:1654-64.
134. Ishitsuka K, Hideshima T, Neri P, et al. p38 mitogen-activated protein kinase inhibitor LY2228820 enhances bortezomib-induced cytotoxicity and inhibits osteoclastogenesis in multiple myeloma; therapeutic implications. Br J Haematol. 2008;141:598-606.
135. Mimnaugh EG, Xu W, Vos M, Yuan X, Neckers L. Endoplasmic reticulum vacuolization and valosin-containing protein relocalization result from simultaneous HSP90 inhibition by geldanamycin and proteasome inhibition by velcade. Mol Cancer Res 2006;4:667-81.
136. Kabeya Y, Mizushima N, Ueno T, Yamamoto A, Kirisako T, Noda T, Kominami E, Ohsumi Y, Yoshimori T. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J 2000;19:5720-8.
137. Ding WX, Ni HM, Gao W, Yoshimori T, Stolz DB, Ron D, Yin XM. Linking of autophagy to ubiquitin-proteasome system is important for the regulation of endoplasmic reticulum stress and cell viability. Am J Pathol 2007;171:513-24.
138. Qing G, Yan P, Xiao G. HSP90 inhibition results in autophagy-mediated proteasome-independent degradation of IkappaB kinase (IKK). Cell Res 2006;16:895-901.
139. Yan P, Qing G, Qu Z, Wu CC, Rabson A, Xiao G. Targeting Autophagic Regulation of NFkappaB in HTLV-I Transformed Cells by Geldanamycin: Implications for Therapeutic Interventions. Autophagy 2007;3:600-3.
140. Maloney A, Workman P. HSP90 as a new therapeutic target for cancer therapy: the story unfolds. Expert Opin Biol Ther 2002;2:3-24.
141. Rutherford SL, Lindquist S. HSP90 as a capacitor for morphological evolution. Nature 1998;396:336-42.
142. Nimmanapalli R, Gerbino E, Dalton WS, Gandhi V, Alsina M. HSP70 inhibition reverses cell adhesion mediated and acquired drug resistance in multiple myeloma. Br J Haematol. 2008;142:551-61.
143. Chatterjee M, Jain S, Stühmer T, et al. STAT3 and MAPK signaling maintain overexpression of heat shock proteins 90α and ß in multiple myeloma cells, which critically contribute to tumor-cell survival. Blood 2007;2:720-8.
144. Isaacs JS, Jung YJ, Mimnaugh EG, Martinez A, Cuttitta F, Neckers LM. HSP90 regulates a von Hippel Lindau-independent hypoxia-inducible factor-1 alpha-degenerative pathway. J Biol Chem 2002;277:29936-44.
145. Sanderson S, Valenti M, Gowan S, Patterson L, Ahmad Z, Workman P, Eccles SA. Benzoquinone ansamycin heat shock protein 90 inhibitors modulate multiple functions required for tumor angiogenesis. Mol Cancer Ther 2006;5:522-32.
146. Medicherla S, Reddy M, Ying J, Navas TA, Li L, Nguyen AN, Kerr I, Hanjarappa N, Protter AA, Higgins LS. p38alpha-selective MAP kinase inhibitor reduces tumor growth in mouse xenograft models of multiple myeloma. Anticancer Res 2009;28:3827-33.
147. Ge F, Lu XP, Zeng HL, He QY, Xiong S, Jin L, He QY. Proteomic and functional analyses reveal a dual molecular mechanism underlying arsenic-induced apoptosis in human multiple myeloma cells. J Proteome Res 2008;8:3006-19.
148. Shammas MA, Koley H, Bertheau RC, et al. Telomerase inhibitor GRN163L inhibits myeloma cell growth in vitro and in vivo. Leukemia 2008;22:1410-8.
149. Davenport EL, Morgan GJ, Davies FE. Perspective Untangling the unfolded protein response. Cell Cycle 2008;7:865-9.
150. Dote H, Cerna D, Burgan WE, Camphausen K, Tofilon PJ. ErbB3 expression predicts tumor cell radiosensitization induced by HSP90 inhibition. Cancer Res 2005;65:6967-9.
151. Harashima K, Akimoto T, Nonaka T, Tsuzuki K, Mitsuhashi N, Nakano T. Heat shock protein 90 (HSP90) chaperone complex inhibitor, radiciol, potentiated radiation-induced cell killing in a hormone-sensitive prostate cancer cell line through degradation of the androgen receptor. Int J Radiat Biol 2005;81:63-76.
152. Camphausen K, Tofilon PJ. Inhibition of HSP90: a multitarged approach to radiosensitization. Clin Cancer Res 2007;13:4326-30.
153. Fionda C, Soriani A, Malgarini G, Iannitto ML, Santoni A, Cippitelli M. Heat Shock Protein-90 Inhibitors Increase MHC Class I-Related Chain A and B Ligand Expression on Multiple Myeloma Cells and Their Ability to Trigger NK Cell Degranulation. J Immunol 2009;183:4385-94.
154. Multhoff G. Activation of natural killer cells by heat shock protein 70. Int J Hyperthermia 2009;25:169-75.
155. Qian J, Hong S, Wang S, Zhang L, Sun L, Wang M, Yang J, Kwak LW, Hou J, Yi Q. Myeloma cell line-derived, pooled heat shock proteins as a universal vaccine for immunotherapy of multiple myeloma. Blood 2009;114:3880-9.
156. Xie Y, Bai O, Zhang H, et al. Membrane-bound HSP70-engineered myeloma cell-derived exosomes stimulate more efficient CD8(+) CTL- and NK-mediated antitumor immunity than exosomes released from heat-shocked tumor cells expressing cytoplasmic HSP70. J Cell Mol Med 2010;14:2655-66.
157. Joly AL, Wettstein G, Mignot G, Ghiringhelli F, Garrido C. Dual role of Heat Shock Proteins as regulators of apoptosis and innate immunity. J Innate Immun 2010;2:238-47.
158. Spisek R, Charalambous A, Mazumder A, Vesole DH, Jagannath S, Madhav V, Dhodapkar MV. Bortezomib enhances dendritic cell (DC)-mediated induction of immunity to human myeloma via exposure of cell surface heat shock protein 90 on dying tumor cells: therapeutic implications. Blood 2007;109:4839-45.
159. Mitsiades N, Mitsiades CS, Poulaki V, et al. Molecular sequelae of proteasome inhibition in human multiple myeloma cells. Proc Natl Acad Sci USA 2002;99:14374-9.
160. Demaria S, Santori FR, Ng B, Liebes L, Formenti SC, Vukmanovic S. Select forms of tumor cell apoptosis induce dendritic cell maturation. J Leukoc Biol 2005;77:361-8.
161. Liu B, Dai J, Zheng H, Stoilova D, Sun S, Li Z. Cell surface expression of an endoplasmic reticulum resident heat shock protein gp96 triggers MyD88-dependent systemic autoimmune diseases. Proc Natl Acad Sci USA 2003;100:15824-9.
162. Dai J, Liu B, Caudill MM, Zheng H, Qiao Y, Podack ER, Li Z. Cell surface expression of heat shock protein gp96 enhances cross-presentation of cellular antigens and the generation of tumor-specific T cell memory. Cancer Immun 2003;3:1.
163. Shen L, Rock KL. Cellular protein is the source of cross-priming antigen in vivo. Proc Natl Acad Sci USA 2004;101:3035-40.
164. Norbury CC, Basta S, Donohue KB, Tscharke DC, Princiotta MF, Berglund P, Gibbs J, Bennink JR, Yewdell JW. CD8+ T cell cross-priming via transfer of proteasome substrates. Science 2004;304:1318-21.
165. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000;100:57-70.
166. Peterson LB, Blagg BS. To fold or not to fold: modulation and consequences of HSP90 inhibition. Future Med Chem 2009;1:267-83.
167. Cirstea D, Vallet S, Raje N. Future novel single agent and combination therapies. Cancer J 2009;15:511-8.
168. Conde R, Belak ZR, Nair M, O'Carroll RF, Ovsenek N. Modulation of Hsf1 activity by novobiocin and geldanamycin. Biochem Cell Biol 2009;87:845-51.
169. Moghimi SM, Hunter AC, Murray JC. Long-circulating and target-specific nanoparticles: theory to practice. Pharmacol Rev 2001;53:283-318.
170. Decuzzi P, Pasqualini R, Arap W, Ferrari M. Intravascular delivery of particulate systems: does geometry really matter? Pharm Res 2009;26:235-43.
171. Chaudhuri P, Harfouche R, Soni S, Hentschel DM, Sengupta S. Shape effect of carbon nanovectors on angiogenesis. ACS Nano 2010;4:574-82.
172. Gratton SE, Ropp PA, Pohlhaus PD, Luft JC, Madden VJ, Napier ME, DeSimone JM. The effect of particle design on cellular internalization pathways. Proc Natl Acad Sci USA 2008;105:11613-8.
173. Cirstea D, Hideshima T, Rodig S, et al. Dual inhibition of akt/mammalian target of rapamycin pathway by nanoparticle albumin-bound-rapamycin and perifosine induces antitumor activity in multiple myeloma. Mol Cancer Ther 2010;9:963-75.
174. Xiong MP, Yáñez JA, Kwon GS, Davies NM, Forrest ML. A cremophor-free formulation for tanespimycin (17-AAG) using PEO-b-PDLLA micelles: characterization and pharmacokinetics in rats. J Pharm Sci 2009;98:1577-86.
175. Bae Y, Buresh RA, Williamson TP, Chen TH, Furgeson DY. Intelligent biosynthetic nanobiomaterials for hyperthermic combination chemotherapy and thermal drug targeting of HSP90 inhibitor geldanamycin. J Control Release 2007;122:16-23.
176. Hung JJ, Wu CY, Liao PC, Chang WC. Hsp90alpha recruited by Sp1 is important for transcription of 12(S)-lipoxygenase in A431 cells. J Biol Chem 2005;280:36283-92.
177. Floer M, Bryant GO, Ptashne M. HSP90/70 chaperones are required for rapid nucleosome removal upon induction of the GAL genes of yeast. Proc Natl Acad Sci USA 2008;105:2975-80.
178. Schnaider T, Oikarinen J, Ishiwatari-Hayasaka H, Yahara I, Csermely P. Interactions of Hsp90 with histones and related peptides. Life Sci 1999;65:2417-26.
179. Csermely P, Kajtar J, Hollosi M, Oikarinen J, Somogyi J. The 90 kDa heat shock protein (hsp90) induces the condensation of the chromatin structure. Biochem Biophys Res Commun 1994;202:1657-63.
180. Tariq M, Nussbaumer U, Chen Y, Beisel C, Paro R. Trithorax requires Hsp90 for maintenance of active chromatin at sites of gene expression. Proc Natl Acad Sci USA 2009;106:1157-62.
181. Fiskus W, Buckley K, Rao R, et al. Panobinostat treatment depletes EZH2 and DNMT1 levels and enhances decitabine mediated de-repression of JunB and loss of survival of human acute leukemia cells. Cancer Biol Ther 2009;8:939-50.
182. Taldone T, Gozman A, Maharaj R, Chiosis G. Targeting Hsp90: small-molecule inhibitors and their clinical development. Curr Opin Pharmacol 2008;8:370-4.
183. Breinig M, Caldas-Lopes E, Goeppert B, Malz M, Rieker R, Bergmann F, Schirmacher P, Mayer M, Chiosis G, Kern MA. Targeting heat shock protein 90 with non-quinone inhibitors: a novel chemotherapeutic approach in human hepatocellular carcinoma. Hepatology 2009;50:102-12.
184. Chiosis G, Lopes EC, Solit D. Heat shock protein-90 inhibitors: a chronicle from geldanamycin to today's agents. Curr Opin Investig Drugs 2006;7:534-41.
185. Schmitt E, Gehrmann M, Brunet M, Multhoff G, Garrido C. Intracellular and extracellular functions of heat shock proteins: repercussions in cancer therapy. J Leukoc Biol 2007;81:15-27.
186. Pespeni M, Hodnett M, Pittet JF. In vivo stress preconditioning. Methods 2005;35:158-64.
187. Shamovsky I, Nudler E. New insights into the mechanism of heat shock response activation. Cell Mol Life Sci 2008;65:855-61.
188. Guettouche T, Boellmann F, Lane WS, Voellmy R. Analysis of phosphorylation of human heat shock factor 1 in cells experiencing a stress. BMC Biochem 2005;6:4.
189. Bagatell R, Paine-Murrieta GD, Taylor CW, Pulcini EJ, Akinaga S, Benjamin IJ, Whitesell L. Induction of a heat shock factor 1-dependent stress response alters the cytotoxic activity of Hsp90-binding agents. Clin Cancer Res 2000;6:3312-8.
190. Demidenko ZN, Vivo C, Halicka HD, Li CJ, Bhalla K, Broude EV, Blagosklonny MV. Pharmacological induction of Hsp70 protects apoptosis-prone cells from doxorubicin: comparison with caspase-inhibitor- and cycle-arrest-mediated cytoprotection. Cell Death Differ 2006;13:1434-41.
191. Martins AS, Ordonez JL, Garcia-Sanchez A, et al. A pivotal role for heat shock protein 90 in Ewing sarcoma resistance to anti-insulin-like growth factor 1 receptor treatment: in vitro and in vivo study. Cancer Res 2008;68:6260-70.
192. Estlin EJ, Veal GJ. Clinical and cellular pharmacology in relation to solid tumours of childhood. Cancer Treat Rev 2003;29:253-73.
193. Cheung CHA, Chen HH, Cheng LT, Lyu KW, Kanwar JR, Chang JY. Targeting Hsp90 with small molecule inhibitors induces the over-expression of the anti-apoptotic molecule, survivin, in human A549, HONE-1 and HT-29 cancer cells. Mol Cancer 2010;9:77.