Heat shock protein 90 inhibition in lung cancer

Journal of Thoracic Oncology

Volumn 3, Issue 6 SUPPL 2, 2008, Pages

  Shimamura, Takeshi ^b   Shapiro, Geoffrey I ^a  

^a DANA FARBER CANCER INSTITUTE   (United States)

^b NONE

Author keywords

Epidermal growth factor receptor; Heat shock protein 90; Lung cancer

Indexed keywords

17 DEMETHOXY 17 (2 DIMETHYLAMINOETHYLAMINO)GELDANAMYCIN; 4 [3 CHLORO 4 (2 PYRIDINYLMETHOXY)ANILINO] 3 CYANO 6 (4 DIMETHYLAMINOCROTONAMIDO) 7 ETHOXYQUINOLINE; B RAF KINASE; BENZYLIDENE DERIVATIVE; BORTEZOMIB; CANERTINIB; CL 387785; CNF 2024; EPIDERMAL GROWTH FACTOR RECEPTOR; EPIDERMAL GROWTH FACTOR RECEPTOR 2; EPIDERMAL GROWTH FACTOR RECEPTOR KINASE INHIBITOR; ERLOTINIB; FLAVOPIRIDOL; GEFITINIB; GELDANAMYCIN; HEAT SHOCK PROTEIN 90; HEAT SHOCK PROTEIN 90 INHIBITOR; HISTONE DEACETYLASE 6; HISTONE DEACETYLASE INHIBITOR; KNK 437; PANOBINOSTAT; RAPAMYCIN; SCATTER FACTOR RECEPTOR; TANESPIMYCIN; TANESPIMYCIN HYDROQUINONE; TRASTUZUMAB; VER 52296;

ABDOMINAL PAIN; AMINO ACID SUBSTITUTION; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; BREAST CANCER; CLINICAL TRIAL; CYTOTOXICITY; DIARRHEA; DRUG EFFICACY; DRUG MECHANISM; DRUG POTENTIATION; GENE MUTATION; HEADACHE; HUMAN; HYPERBILIRUBINEMIA; LUNG ADENOCARCINOMA; LUNG NON SMALL CELL CANCER; LUNG SMALL CELL CANCER; NAUSEA; NONHUMAN; PRIORITY JOURNAL; REVIEW; SIDE EFFECT; SIGNAL TRANSDUCTION; UNSPECIFIED SIDE EFFECT; VOMITING;

EID: 44649139884     PISSN: 15560864     EISSN: 15561380     Source Type: Journal    
DOI: 10.1097/JTO.0b013e318174ea3a     Document Type: Article

References (107)

1. Pratt WB. The hsp90-based chaperone system: involvement in signal transduction from a variety of hormone and growth factor receptors. Proc Soc Exp Biol Med 1998;217:420-434.
2. Whitesell L, Lindquist SL. HSP90 and the chaperoning of cancer. Nat Rev Cancer 2005;5:761-772.
3. Leppa S, Sistonen L. Heat shock response: pathophysiological implications. Ann Med 1997;29:73-78.
4. Sepp-Lorenzino L, Ma Z, Lebwohl DE, Vintsky A, Rosen N. Herbimycin A induces the 20 S proteasome- and ubiquitin-dependent degradation of receptor tyrosine kinases. J Biol Chem 1995;270:16580-16587.
5. Workman P. Altered states: selectively drugging the Hsp90 cancer chaperone. Trends Mol Med 2004;10:47-51.
6. Jolly C, Morimoto RI. Role of the heat shock response and molecular chaperones in oncogenesis and cell death. J Natl Cancer Inst 2000;92:1564-1572.
7. Weinstein IB. Addiction to oncogenes-the Achilles heal of cancer. Science 2002;297:63-64.
8. 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;13:1625-1629.
9. Bishop SC, Burlison JA, Blagg BS. Hsp90: a novel target for the disruption of multiple signaling cascades. Curr Cancer Drug Targets 2007;7:369-388.
10. Xu Y, Singer MA, Lindquist S. Maturation of the tyrosine kinase c-src as a kinase and as a substrate depends on the molecular chaperone Hsp90. Proc Natl Acad Sci USA 1999;96:109-114.
11. da Rocha Dias S, Friedlos F, Light Y, Springer C, Workman P, Marais R. Activated B-RAF is an Hsp90 client protein that is targeted by the anticancer drug 17-allylamino-17-demethoxygeldanamycin. Cancer Res 2005;65:10686-10691.
12. Grbovic OM, Basso AD, Sawai A, et al. V600E B-Raf requires the Hsp90 chaperone for stability and is degraded in response to Hsp90 inhibitors. Proc Natl Acad Sci USA 2006;103:57-62.
13. Kamal A, Thao L, Sensintaffar J, et al. A high-affinity conformation of Hsp90 confers tumour selectivity on Hsp90 inhibitors. Nature 2003;425:407-410.
14. Egorin MJ, Lagattuta TF, Hamburger DR, et al. Pharmacokinetics, tissue distribution, and metabolism of 17-(dimethylaminoethylamino)-17- demethoxygeldanamycin (NSC 707545) in CD2F1 mice and Fischer 344 rats. Cancer Chemother Pharmacol 2002;49:7-19.
15. Xu L, Eiseman JL, Egorin MJ, D'Argenio DZ. Physiologically-based pharmacokinetics and molecular pharmacodynamics of 17-(allylamino)-17- demethoxygeldanamycin and its active metabolite in tumor-bearing mice. J Pharmacokinet Pharmacodyn 2003;30:185-219.
16. Shimamura T, Lowell AM, Engelman JA, Shapiro GI. Epidermal growth factor receptors harboring kinase domain mutations associate with the heat shock protein 90 chaperone and are destabilized following exposure to geldanamycins. Cancer Res 2005;65:6401-6408.
17. Janne PA, Engelman JA, Johnson BE. Epidermal growth factor receptor mutations in non-small-cell lung cancer: implications for treatment and tumor biology. J Clin Oncol 2005;23:3227-3234.
18. Paez JG, Janne PA, Lee JC, et al. EGFR mutations in lung cancer: correlation with clinical response to Gefitinib therapy. Science 2004;304:1497-1500.
19. Lynch TJ, Bell DW, Sordella R, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 2004;350:2129-2139.
20. Pao W, Miller V, Zakowski M, et al. EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci USA 2004;101:13306-13311.
21. Yang S, Qu S, Perez-Tores M, et al. Association with HSP90 inhibits Cbl-mediated down-regulation of mutant epidermal growth factor receptors. Cancer Res 2006;66:6990-6997.
22. Xu W, Mimnaugh E, Rosser MF, et al. Sensitivity of mature Erbb2 to geldanamycin is conferred by its kinase domain and is mediated by the chaperone protein Hsp90. J Biol Chem 2001;276:3702-3708.
23. Greulich H, Chen TH, Feng W, et al. Oncogenic transformation by inhibitor-sensitive and -resistant EGFR mutants. PLoS Med 2005;2:e313.
24. Xu W, Soga S, Beebe K, et al. Sensitivity of epidermal growth factor receptor and ErbB2 exon 20 insertion mutants to Hsp90 inhibition. Br J Cancer 2007;97:741-744.
25. Kobayashi S, Boggon TJ, Dayaram T, et al. EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N Engl J Med 2005;352:786-792.
26. Pao W, Miller VA, Politi KA, et al. Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med 2005;2:1-11.
27. Mulloy R, Ferrand A, Kim Y, et al. Epidermal growth factor receptor mutants from human lung cancers exhibit enhanced catalytic activity and increased sensitivity to gefitinib. Cancer Res 2007;67:2325-2330.
28. Kobayashi S, Ji H, Yuza Y, et al. An alternative inhibitor overcomes resistance caused by a mutation of the epidermal growth factor receptor. Cancer Res 2005;65:7096-7101.
29. Kwak EL, Sordella R, Bell DW, et al. Irreversible inhibitors of the EGF receptor may circumvent acquired resistance to gefitinib. Proc Natl Acad Sci USA 2005;102:7665-7670.
30. Carter TA, Wodicka LM, Shah NP, et al. Inhibition of drug-resistant mutants of ABL, KIT, and EGF receptor kinases. Proc Natl Acad Sci USA 2005;102:11011-11016.
31. Li D, Shimamura T, Ji H, et al. Bronchial and peripheral murine lung carcinomas induced by T790M-L858R mutant EGFR respond to HKI-272 and rapamycin combination therapy. Cancer Cell 2007;12:81-93.
32. Regales L, Balak MN, Gong Y, et al. Development of new mouse lung tumor models expressing EGFR T790M mutants associated with clinical resistance to kinase inhibitors. PLoS ONE 2007;2:e810.
33. Wong KK, Fracasso PM, Bukowski RM, et al. HKI-272, an irreversible pan erbB receptor tyrosine kinase inhibitor: preliminary phase I results in patients with solid tumors (abstract). Proc Am Soc Clin Oncol 2006;24:A3018.
34. Basso AD, Solit DB, Chiosis G, Giri B, Tsichlis P, Rosen N. 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;277:39858-39866.
35. Ohji G, Hidayat S, Nakashima A, et al. Suppression of the mTOR-raptor signaling pathway by the inhibitor of heat shock protein 90 geldanamycin. J Biochem (Tokyo) 2006;139:129-135.
36. Shimamura T, Li D, Ji H, et al. Hsp90 inhibition suppresses mutant EGFR-T790M signaling and overcomes kinase inhibitor release. Cancer Res 2008, in press.
37. Ji H, Zhao X, Yuza Y, et al. Epidermal growth factor receptor variant III mutations in lung tumorigenesis and sensitivity to tyrosine kinase inhibitors. Proc Natl Acad Sci USA 2006;103:7817-7822.
38. Lavictoire SJ, Parolin DA, Klimowicz AC, Kelly JF, Lorimer IA. Interaction of Hsp90 with the nascent form of the mutant epidermal growth factor receptor EGFRvIII. J Biol Chem 2003;278:5292-5299.
39. Stephens P, Hunter C, Bignell G, et al. Lung cancer: intragenic ERBB2 kinase mutations in tumours. Nature 2004;431:525-526.
40. Shigematsu H, Takahashi T, Nomura M, et al. Somatic mutations of the HER2 kinase domain in lung adenocarcinomas. Cancer Res 2005;65:1642-1646.
41. Shimamura T, Ji H, Minami Y, et al. Non-small-cell lung cancer and Ba/F3 transformed cells harboring the ERBB2 G776insV_G/C mutation are sensitive to the dual-specific epidermal growth factor receptor and ERBB2 inhibitor HKI-272. Cancer Res 2006;66:6487- 6491.
42. Webb CP, Hose CD, Koochekpour S, et al. The geldanamycins are potent inhibitors of the hepatocyte growth factor/scatter factor-meturokinase plasminogen activator-plasmin proteolytic network. Cancer Res 2000;60:342-349.
43. Shen Y, Xie Q, Norberg M, Sausville E, Woude GV, Wenkert D. Geldanamycin derivative inhibition of HGF/SF-mediated Met tyrosine kinase receptor-dependent urokinase-plasminogen activation. Bioorg Med Chem 2005;13:4960-4971.
44. Maulik G, Kijima T, Ma PC, et al. Modulation of the c-Met/Hepatocyte growth factor pathway in small cell lung cancer. Clin Cancer Res 2002;8:620-627.
45. Brose MS, Volpe P, Feldman M, et al. BRAF and RAS mutations in human lung cancer and melanoma. Cancer Res 2002;62:6997-7000.
46. Naoki K, Chen TH, Richards WG, Sugarbaker DJ, Meyerson M. Missense mutations of the BRAF gene in human lung adenocarcinoma. Cancer Res 2002;62:7001-7003.
47. Ma PC, Jagadeeswaran R, Jagadeesh S, et al. Functional expression and mutations of c-Met and its therapeutic inhibition with SU11274 and small interfering RNA in non-small cell lung cancer. Cancer Res 2005;65:1479-1488.
48. Kong-Beltran M, Seshagiri S, Zha J, et al. Somatic mutations lead to an oncogenic deletion of met in lung cancer. Cancer Res 2006;66:283-289.
49. Zhao X, Weir BA, LaFramboise T, et al. Homozygous deletions and chromosome amplifications in human lung carcinomas revealed by single nucleotide polymorphism array analysis. Cancer Res 2005;65:5561-5570.
50. Lutterbach B, Zeng Q, Davis LJ, et al. Lung cancer cell lines harboring MET gene amplification are dependent on Met for growth and survival. Cancer Res 2007;67:2081-2088.
51. Smolen GA, Sordella R, Muir B, et al. Amplification of MET may identify a subset of cancers with extreme sensitivity to the selective tyrosine kinase inhibitor PHA-665752. Proc Natl Acad Sci USA 2006;103:2316-2321.
52. Engelman JA, Zejnullahu K, Mitsudomi T, et al. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science 2007;316:1039-1043.
53. Wikman H, Nymark P, Vayrynen A, et al. CDK4 is a probable target gene in a novel amplicon at 12q13. 3-q14. 1 in lung cancer. Genes Chromosomes Cancer 2005;42:193-199.
54. Morgillo F, Woo JK, Kim ES, Hong WK, Lee HY. Heterodimerization of insulin-like growth factor receptor/epidermal growth factor receptor and induction of survivin expression counteract the antitumor action of erlotinib. Cancer Res 2006;66:10100-10111.
55. Mitsiades CS, Mitsiades NS, McMullan CJ, et al. Antimyeloma activity of heat shock protein-90 inhibition. Blood 2006;107:1092-1100.
56. Verdin E, Dequiedt F, Kasler HG. Class II histone deacetylases: versatile regulators. Trends Genet 2003;19:286-293.
57. Hubbert C, Guardiola A, Shao R, et al. HDAC6 is a microtubule-associated deacetylase. Nature 2002;417:455-458.
58. 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;280:26729-26734.
59. Boyault C, Sadoul K, Pabion M, Khochbin S. HDAC6, at the crossroads between cytoskeleton and cell signaling by acetylation and ubiquitination. Oncogene 2007;26:5468-5476.
60. Kawaguchi Y, Kovacs JJ, McLaurin A, Vance JM, Ito A, Yao TP. The deacetylase HDAC6 regulates aggresome formation and cell viability in response to misfolded protein stress. Cell 2003;115:727-738.
61. Nimmanapalli R, Fuino L, Bali P, et al. Histone deacetylase inhibitor LAQ824 both lowers expression and promotes proteasomal degradation of Bcr-Abl and induces apoptosis of imatinib mesylate-sensitive or -refractory chronic myelogenous leukemia-blast crisis cells. Cancer Res 2003;63:5126-5135.
62. Fuino L, Bali P, Wittmann S, et al. Histone deacetylase inhibitor LAQ824 down-regulates Her-2 and sensitizes human breast cancer cells to trastuzumab, taxotere, gemcitabine, and epothilone B. Mol Cancer Ther 2003;2:971-984.
63. 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;105:1768-1776.
64. Edwards A, Li J, Atadja P, Bhalla K, Haura EB. Effect of the histone deacetylase inhibitor LBH589 against epidermal growth factor receptor-dependent human lung cancer cells. Mol Cancer Ther 2007;6:2515-2524.
65. Fribley A, Wang CY. Proteasome inhibitor induces apoptosis through induction of endoplasmic reticulum stress. Cancer Biol Ther 2006;5:745-748.
66. Nawrocki ST, Carew JS, Pino MS, et al. Bortezomib sensitizes pancreatic cancer cells to endoplasmic reticulum stress-mediated apoptosis. Cancer Res 2005;65:11658-11666.
67. 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;107:4907-4916.
68. Boelens J, Lust S, Offner F, Bracke ME, Vanhoecke BW. Review. The endoplasmic reticulum: a target for new anticancer drugs. In Vivo 2007;21:215-226.
69. Fanucchi MP, Fossella FV, Belt R, et al. Randomized phase II study of bortezomib alone and bortezomib in combination with docetaxel in previously treated advanced non-small-cell lung cancer. J Clin Oncol 2006;24:5025-5033.
70. Garrido C, Schmitt E, Cande C, Vahsen N, Parcellier A, Kroemer G. HSP27 and HSP70: potentially oncogenic apoptosis inhibitors. Cell Cycle 2003;2:579-584.
71. Garrido C, Brunet M, Didelot C, Zermati Y, Schmitt E, Kroemer G. Heat shock proteins 27 and 70: anti-apoptotic proteins with tumorigenic properties. Cell Cycle 2006;5:2592-2601.
72. Ravagnan L, Gurbuxani S, Susin SA, et al. Heat-shock protein 70 antagonizes apoptosis-inducing factor. Nat Cell Biol 2001;3:839-843.
73. Saleh A, Srinivasula SM, Balkir L, Robbins PD, Alnemri ES. Negative regulation of the Apaf-1 apoptosome by Hsp70. Nat Cell Biol 2000;2:476-483.
74. Beere HM, Wolf BB, Cain K, et al. Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome. Nat Cell Biol 2000;2:469-475.
75. Guo F, Rocha K, Bali P, et al. Abrogation of heat shock protein 70 induction as a strategy to increase antileukemia activity of heat shock protein 90 inhibitor 17-allylamino-demethoxy geldanamycin. Cancer Res 2005;65:10536-10544.
76. Ni Z, Schwartz BE, Werner J, Suarez JR, Lis JT. Coordination of transcription, RNA processing, and surveillance by P-TEFb kinase on heat shock genes. Mol Cell 2004;13:55-65.
77. Garriga J, Grana X. Cellular control of gene expression by T-type cyclin/CDK9 complexes. Gene 2004;337:15-23.
78. Shapiro GI. Cyclin-dependent kinase pathways as targets for cancer treatment. J Clin Oncol 2006;24:1770-1783.
79. Chao SH, Fujinaga K, Marion JE, et al. Flavopiridol inhibits P-TEFb and blocks HIV-1 replication. J Biol Chem 2000;275:28345-28348.
80. Chao SH, Price DH. Flavopiridol inactivates p-TEFb and blocks most RNA polymerase II transcription in vivo. J Biol Chem 2001;276:31793-31799.
81. Lam LT, Pickeral OK, Peng AC, et al. Genomic-scale measurement of mRNA turnover and the mechanisms of action of the anti-cancer drug flavopiridol. Genome Biol 2001;2:RESEARCH0041.
82. Demidenko ZN, Vivo C, Halicka HD, et al. Pharmacological induction of Hsp70 protects apoptosis-prone cells from doxorubicin: comparison with caspase-inhibitor- and cycle-arrest-mediated cytoprotection. Cell Death Differ 2006;13:1434-1441.
83. Rodina A, Vilenchik M, Moulick K, et al. Selective compounds define Hsp90 as a major inhibitor of apoptosis in small-cell lung cancer. Nat Chem Biol 2007;3:498-507.
84. Sausville EA, Tomaszewski JE, Ivy P. Clinical development of 17-allylamino, 17-demethoxygeldanamycin. Curr Cancer Drug Targets 2003;3:377-383.
85. Banerji U, O'Donnell A, Scurr M, et al. Phase I pharmacokinetic and pharmacodynamic study of 17-allylamino, 17-demethoxygeldanamycin in patients with advanced malignancies. J Clin Oncol 2005;23:4152-4161.
86. 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;23:1078-1087.
87. 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;11:3385-3391.
88. 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;23:1885-1893.
89. Nowakowski GS, McCollum AK, Ames MM, et al. A phase I trial of twice-weekly 17-allylamino-demethoxy-geldanamycin in patients with advanced cancer. Clin Cancer Res 2006;12:6087-6093.
90. 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;13:1769-1774.
91. 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;13:1775-1782.
92. Bagatell R, Gore L, Egorin MJ, et al. Phase I pharmacokinetic and pharmacodynamic study of 17-N-allylamino-17-demethoxygeldanamycin in pediatric patients with recurrent or refractory solid tumors: a pediatric oncology experimental therapeutics investigators consortium study. Clin Cancer Res 2007;13:1783-1788.
93. Weigel BJ, Blaney SM, Reid JM, et al. A phase I study of 17-allylaminogeldanamycin in relapsed/refractory pediatric patients with solid tumors: a Children's Oncology Group study. Clin Cancer Res 2007;13:1789-1793.
94. Tian ZQ, Liu Y, Zhang D, et al. Synthesis and biological activities of novel 17-aminogeldanamycin derivatives. Bioorg Med Chem 2004;12:5317-5329.
95. Eiseman JL, Lan J, Lagattuta TF, et al. Pharmacokinetics and pharmacodynamics of 17-demethoxy 17-[[(2-dimethylamino)ethyl]amino]-geldanamycin (17DMAG, NSC 707545) in C.B-17 SCID mice bearing MDA-MB-231 human breast cancer xenografts. Cancer Chemother Pharmacol 2005;55:21-32.
96. Smith V, Sausville EA, Camalier RF, Fiebig HH, Burger AM. Comparison of 17-dimethylaminoethylamino-17-demethoxy-geldanamycin (17DMAG) and 17-allylamino-17-demethoxygeldanamycin (17AAG) in vitro: effects on Hsp90 and client proteins in melanoma models. Cancer Chemother Pharmacol 2005;56:126-137.
97. 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;49:4606-4615.
98. 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;103:17408-17413.
99. Shadad FN, Ramanathan RK. 17-dimethylaminoethylamino-17- demethoxygeldanamycin in patients with advanced-stage solid tumors and lymphoma: a phase I study. Clin Lymphoma Myeloma 2006;6:500-501.
100. Cartwright EP, Kummar S, Muir CA, et al. Interim analysis of phase I trial of 17-DMAG (abstract). Proc Am Soc Clin Oncol 2006;24:A13148.
101. Lancet J, Gojo I, Baer M, et al. Phase 1, pharmacokinetic (PK) and pharmacodynamic (PD) study of the Hsp90 inhibitor KOS-1022 (17-DMAG) in patients with refractory hemtological malignancies (abstract). Proc Am Soc Clin Oncol 2006;24:A2081.
102. Demetri GD, George S, Morgan JA, et al. Overcoming resistance to tyrosine kinase inhibitors (TKIs) through inhibition of Heat Shock Protein (Hsp90) chaperone function in patients with metastatic GIST: results of a Phase I Trial of IPI-504, a water-soluble Hsp90 inhibitor (abstract). Eur J Cancer 2006;4:A570.
103. Modi S, Stopeck AT, Gordon MS, et al. Combination of trastuzumab and tanespimycin (17-AAG, KOS-953) is safe and active in trastuzumab-refractory HER-2 overexpressing breast cancer: a phase I dose-escalation study. J Clin Oncol 2007;25:5410-5417.
104. Sequist L, Janne PA, Walker J, Sweeney J, Grayzel D, Lynch TJ. Phase I/II trial of the novel Hsp90 inhibitor, IPI-504, inpatients with relapsed and/or refractory stage IIIB or stage IV non-small cell lung cancer stratified by EGFR mutation status (abstract). Proc AACR-NCI-EORTC 2007:B29.
105. Sharp S, Workman P. Inhibitors of the HSP90 molecular chaperone: current status. Adv Cancer Res 2006;95:323-348.
106. Chiosis G, Lucas B, Shtil A, Huezo H, Rosen N. Development of a purine-scaffold novel class of Hsp90 binders that inhibit the proliferation of cancer cells and induce the degradation of Her2 tyrosine kinase. Bioorg Med Chem 2002;10:3555-3564.
107. Brough PA, Aherne W, Barril X, et al. 4,5-Diarylisoxazole Hsp90 chaperone inhibitors: potential therapeutic agents for the treatment of cancer. J Med Chem 2008;51:196-218.