Hsp90: A novel target for cancer therapy

Current Topics in Medicinal Chemistry

Volumn 6, Issue 11, 2006, Pages 1205-1214

  Solit, David B ^a   Rosen, Neal ^a  

^a MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

Author keywords

Cytotoxics; Docetaxel; Energy transfer; HER2; Hormone refractory prostate cancer; RB Negative Tumors

Indexed keywords

17 ALLYLAMINO 17 DEMETHOXYGELDANAMYCIN; 17 DIMETHYLAMINOEOTHYLAMINO 17DEMETHOXYGELDANAMYCIN; 2 MORPHOLINO 8 PHENYLCHROMONE; 7 ETHYL 10 HYDROXYCAMPTOTHECIN; 7 HYDROXYSTAUROSPORINE; ANSAMYCIN DERIVATIVE; BORTEZOMIB; BUTYRIC ACID; CHAPERONE; CISPLATIN; CNF 1010; CYTARABINE; CYTOTOXIC AGENT; DOCETAXEL; DOXORUBICIN; EPIDERMAL GROWTH FACTOR RECEPTOR 2; FLUDARABINE; HEAT SHOCK PROTEIN 90; HEAT SHOCK PROTEIN 90 INHIBITOR; IMATINIB; IRINOTECAN; MIDOSTAURIN; MUTANT PROTEIN; NATURAL PRODUCT; ONCOPROTEIN; PACLITAXEL; RITUXIMAB; TRASTUZUMAB; UNCLASSIFIED DRUG; UNINDEXED DRUG; VORINOSTAT;

ADVANCED CANCER; ANTINEOPLASTIC ACTIVITY; BREAST CANCER; CANCER CELL; CANCER THERAPY; CELL SURVIVAL; CHRONIC MYELOID LEUKEMIA; CLINICAL TRIAL; COMPLEX FORMATION; DRUG CYTOTOXICITY; DRUG POTENTIATION; DRUG STRUCTURE; DRUG USE; HEMATOLOGIC MALIGNANCY; HUMAN; IN VIVO STUDY; KIDNEY CANCER; MASTOCYTOSIS; MELANOMA; MULTIPLE CANCER; NONHUMAN; OVARY CANCER; PHARMACODYNAMICS; PHENOTYPE; PHYSICAL CHEMISTRY; PROTEIN BINDING; PROTEIN CONFORMATION; PROTEIN DEGRADATION; PROTEIN FOLDING; PROTEIN FUNCTION; PROTEIN PROCESSING; REVIEW; SOLID TUMOR; STRESS; THYROID CANCER; UNSPECIFIED SIDE EFFECT;

ANIMALS; ANTINEOPLASTIC AGENTS; CLINICAL TRIALS; COMBINED MODALITY THERAPY; DRUG DESIGN; HSP90 HEAT-SHOCK PROTEINS; HUMANS; MOLECULAR STRUCTURE; NEOPLASMS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 33746417580     PISSN: 15680266     EISSN: None     Source Type: Journal    
DOI: 10.2174/156802606777812068     Document Type: Review

References (103)

1. DeBoer, C.; Meulman, P. A.; Wnuk, R. J.; Peterson, D. H. Geldanamycin, a new antibiotic. J. Antibiot. (Tokyo) 1970, 23, 442-447.
2. Uehara, Y.; Hori, M.; Takeuchi, T.; Umezawa, H. Screening of agents which convert 'transformed morphology' of Rous sarcoma virus-infected rat kidney cells to 'normal morphology': identification of an active agent as herbimycin and its inhibition of intracellular src kinase. Jpn. J. Cancer Res. 1985, 76, 672-675.
3. Whitesell, L.; Mimnaugh, E. G.; De Costa, B.; Myers, C. E.; Neckers, L. M. 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, 8324-8328.
4. Sepp-Lorenzino, L.; Ma, Z.; Lebwohl, D. E.; Vinitsky, 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. Stebbins, C. E.; Russo, A. A.; Schneider, C.; Rosen, N.; Hartl, F. U.; Pavletich, N. P. Crystal structure of an Hsp90-geldanamycin complex: targeting of a protein chaperone by an antitumor agent. Cell 1997, 89, 239-250.
6. Prodromou, C.; Roe, S. M.; O'Brien, R.; Ladbury, J. E.; Piper, P. W.; Pearl, L. H. Identification and structural characterization of the ATP/ ADP-binding site in the Hsp90 molecular chaperone. Cell 1997, 90, 65-75.
7. Schulte, T. W.; Akinaga, S.; Soga, S.; Sullivan, W.; Stensgard, B.; Toft, D.; Neckers, L. M. Antibiotic radicicol binds to the N-terminal domain of Hsp90 and shares important biologic activities with geldanamycin. Cell Stress Chaperones 1998, 3, 100-108.
8. Schneider, C.; Sepp-Lorenzino, L.; Nimmesgern, E.; Ouerfelli, O.; Danishefsky, S.; Rosen, N.; Hartl, F. U. Pharmacologic shifting of a balance between protein refolding and degradation mediated by Hsp90. Proc. Natl. Acad. Sci. USA 1996, 93, 14536-14541.
9. Whitesell, L.; Cook, P. Stable and specific binding of heat shock protein 90 by geldanamycin disrupts glucocorticoid receptor function in intact cells. Mol. Endocrinol. 1996, 10, 705-712.
10. Schulte, T. W.; Blagosklonny, M. V.; Ingui, C.; Neckers, L. Disruption of the Raf-1-Hsp90 molecular complex results in destabilization of Raf-1 and loss of Raf-1-Ras association. J. Biol. Chem. 1995, 270, 24585-24588.
11. Scheibel, T.; Siegmund, H. I.; Jaenicke, R.; Ganz, P.; Lilie, H.; Buchner, J. The charged region of Hsp90 modulates the function of the N-terminal domain. Proc. Natl. Acad Sci. USA 1999, 96, 1297-1302.
12. Fang, Y.; Fliss, A. E.; Robins, D. M.; Caplan, A. J. Hsp90 regulates androgen receptor hormone binding affinity in vivo. J. Biol. Chem. 1996, 271, 28697-28702.
13. Vilenchik, M.; Solit, D.; Basso, A.; Huezo, H.; Lucas, B.; He, H.; Rosen, N.; Spampinato, C.; Modrich, P.; Chiosis, G. Targeting wide-range oncogenic transformation via PU24FCI, a specific inhibitor of tumor Hsp90. Chem. Biol. 2004, 11, 787-797.
14. Kamal, A.; Thao, L.; Sensintaffar, J.; Zhang, L.; Boehm, M. F.; Fritz, L. C.; Burrows, F. J. A high-affinity conformation of Hsp90 confers tumour selectivity on Hsp90 inhibitors. Nature 2003, 425, 407-410.
15. Banerji, U.; O'Donnell, A.; Scurr, M.; Pacey, S.; Stapleton, S.; Asad, Y.; Simmons, L.; Maloney, A.; Raynaud, F.; Campbell, M.; Walton, M.; Lakhani, S.; Kaye, S.; Workman, P.; Judson, I. Phase I pharmacokinetic and pharmacodynamic study of 17-allylamino, 17-demethoxygeldanamycin in patients with advanced malignancies. J. Clin. Oncol. 2005, 23, 4152-4161.
16. Goetz, M. P.; Toft, D.; Reid, J.; Ames, M.; Stensgard, B.; Safgren, S.; Adjei, A. A.; Sloan, J.; Atherton, P.; Vasile, V.; Salazaar, S.; Adjei, A.; Croghan, G.; Erlichman, C. Phase I trial of 17-allylamino-17-demethoxygeldanamycin in patients with advanced cancer. J. Clin. Oncol. 2005, 23, 1078-1087.
17. Grem, J. L.; Morrison, G.; Guo, X. D.; Agnew, E.; Takimoto, C. H.; Thomas, R.; Szabo, E.; Grochow, L.; Grollman, F.; Hamilton, J. M.; Neckers, L.; Wilson, R. H. Phase I and pharmacologic study of 17-(allylamino)-17-demethoxygeldanamycin in adult patients with solid tumors. J. Clin. Oncol. 2005, 23, 1885-1893.
18. Ramanathan, R. K.; Trump, D. L.; Eiseman, J. L.; Belani, C. P.; Agarwala, S. S.; Zuhowski, E. G.; Lan, J.; Potter, D. M.; Ivy, S. P.; Ramalingam, S.; Brufsky, A. M.; Wong, M. K.; Tutchko, S.; Egorin, M. J. Phase I pharmacokinetic-pharmacodynainic 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.
19. Solit, D.; Kelly, W.; Anana, M.; De La Cruz, A.; Valentin, G.; Tong, W.; Morris, M.; Slovin, S.; Busam, K.; Lawrence, S.; Larson, S.; Reuter, V.; Rosen, N.; Scher, H. Phase I trial of 17-AAG (17-allylamino-17-demethoxygeldanamycin) in patients (Pts) with advanced cancer. Proc. Am. Soc. Clin. Oncol. 2003, 22, 198.
20. Supko, J. G.; Hickman, R. L.; Grever, M. R.; Malspeis, L. Preclinical pharmacologic evaluation of geldanamycin as an antitumor agent. Cancer Chemother. Pharmacol. 1995, 36, 305-315.
21. Solit, D. B.; Zheng, F. F.; Drobnjak, M.; Munster, P. N.; Higgins, B.; Verbel, D.; Heller, G.; Tong, W.; Cordon-Cardo, C.; Agus, D. B.; Scher, H. I.; Rosen, N. 17-Allylamino-17-demethoxy-geldanamycin induces the degradation of androgen receptor and HER-2/neu and inhibits the growth of prostate cancer xenografts. Clin. Cancer Res. 2002, 8, 986-993.
22. Solit, D. B.; Basso, A. D.; Olshen, A. B.; Scher, H. I.; Rosen, N. Inhibition of heat shock protein 90 function down-regulates akt kinase and sensitizes tumors to taxol. Cancer Res. 2003, 63, 2139-2144.
23. de Candia, P.; Solit, D. B.; Giri, D.; Brogi, E.; Siegel, P. M.; Olshen, A. B.; Muller, W. J.; Rosen, N.; Benezra, R. Angiogenesis impairment in Id-deficient mice cooperates with an Hsp90 inhibitor to completely suppress HER2/neu-dependent breast tumors. Proc. Natl. Acad. Sci. USA 2003, 100, 12337-12342.
24. Munster, P. N.; Marchion, D. C.; Basso, A. D.; Rosen, N. Degradation of HER2 by ansamycins induces growth arrest and apoptosis in cells with HER2 overexpression via a HER3, phosphatidylinositol 3'-kinase-AKT-dependent pathway. Cancer Res. 2002, 62, 3132-3137.
25. Webb, C. P.; Hose, C. D.; Koochekpour, S.; Jeffers, M.; Oskarsson, M.; Sausville, E.; Monks, A.; Vande Woude, G. F. The geldanamycins are potent inhibitors of the hepatocyte growth factor/scatter factor-met-urokinase plasminogen activator-plasmin proteolytic network. Cancer Res. 2000, 60, 342-349.
26. Basso, A.; Solit, D.; Munster, P.; Rosen, N. Ansamycin antibiotics inhibit Akt activation and tumor growth in human breast cancers that overexpress HER2. Oncogene 2002, 21, 1159-1166.
27. Basso, A. D.; Solit, D. B.; 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.
28. Munster, P. N.; Basso, A.; Solit, D.; Norton, L.; Rosen, N. Modulation of Hsp90 function by ansamycins sensitizes breast cancer cells to chemotherapy-induced apoptosis in an RB- and schedule- dependent manner. Clin. Cancer Res. 2001, 7. 2228-2236.
29. Enmon, R.; Yang, W. H.; Ballangrud, A. M.; Solit, D. B.; Heller, G.; Rosen, N.; Scher, H. I.; Sgouros, G. Combination treatment with 17-N-allylamino-17-demethoxy geldanamycin and acute irradiation produces supra-additive growth suppression in human prostate carcinoma spheroids. Cancer Res. 2003, 63, 8393-8399.
30. Scher, H. I.; Sawyers, C. L. Biology of progressive, castration-resistant prostate cancer: directed therapies targeting the androgen-receptor signaling axis. J. Clin. Oncol. 2005, 23, 8253-8261.
31. Solit, D. B.; Scher, H. I.; Rosen, N. Hsp90 as a therapeutic target in prostate cancer. Semin. Oncol. 2003, 30, 709-716.
32. Craft, N.; Shostak, Y.; Carey, M.; Sawyers, C. L. A mechanism for hormone-independent prostate cancer through modulation of androgen receptor signaling by the HER-2/neu tyrosine kinase. Nat. Med. 1999, 5, 280-285.
33. Mellinghoff, I. K.; Vivanco, I.; Kwon, A.; Tran, C.; Wongvipat, J.; Sawyers, C. L. HER2/neu kinase-dependent modulation of androgen receptor function through effects on DNA binding and stability. Cancer Cell 2004, 6, 517-527.
34. Gorre, M. E.; Ellwood-Yen, K.; Chiosis, G.; Rosen, N.; Sawyers, C. L. BCR-ABL point mutants isolated from patients with imatinib mesylate-resistant chronic myeloid leukemia remain sensitive to inhibitors of the BCR-ABL chaperone heat shock protein 90. Blood 2002, 100, 3041-3044.
35. 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-demethoxy-geldanamycin. Cancer Res. 2005, 65, 10686-10691.
36. Grbovic, O. M.; Basso, A. D.; Sawai, A.; Ye, Q.; Friedlander, P.; Solit, D.; Rosen, N. 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.
37. Shimamura, T.; Lowell, A. M.; Engelman, J. A.; Shapiro, G. I. 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.
38. Datta, S. R.; Brunet, A.; Greenberg, M. E. Cellular survival: a play in dure Akts. Genes Dev. 1999, 13, 2905-2927.
39. Nguyen, D. M.; Chen, A.; Mixon, A.; Schrump, D. S. Sequence-dependent enhancement of paclitaxel toxicity in non-small cell lung cancer by 17-allylamino 17-demethoxygeldanamycin. J. Thorac. Cardiovasc. Surg. 1999, 118, 908-915.
40. Tse, A.; Sheikh, T.; Schwartz, G. The Hsp90 inhibitor, 17-Allyl-amino-17-Demethoxygeldanamycin (17AAG) abrogates the G2/M DNA damage checkpoint and induces apoptosis selectively in p53-defective colon cancer cells by down-regulating both Chk1 and Weel. Proc. Amer. Assoc. Cancer Res. 2005, 46, 1449.
41. Mabjeesh, N. J.; Post, D. E.; Willard, M. T.; Kaur, B.; Van Meir, E. G.; Simons, J. W.; Zhong, H. Geldanamycin induces degradation of hypoxia-inducible factor lalpha protein via the proteosome pathway in prostate cancer cells. Cancer Res. 2002, 62, 2478-2482.
42. Kaur, G.; Belotti, D.; Burger, A. M.; Fisher-Nielson, K.; Borsotti, P.; Riccardi, E.; Thillainathan, J.; Hollingshead, M.; Sausville, E. A.; Giavazzi, R. Antiangiogenic properties of 17-(dimethyl-aminoethylamino)-17-demethoxygeldanainycin: an orally bio-available heat shock protein 90 modulator. Clin. Cancer Res. 2004, 10, 4813-4821.
43. 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, 3940-3946.
44. Burrows, F.; Zhang, H.; Kamal, A. Hsp90 activation and cell cycle regulation. Cell Cycle 2004, 3, 1530-1536.
45. Munster, P. N.; Srethapakdi, M.; Moasser, M. M.; 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, 2945-2952.
46. Eiseman, J. L.; Lan, J.; Lagattuta, T. F.; Hamburger, D. R.; Joseph, E.; Covey, J. M.; Egorin, M. J. Pharmacokinetics and pharmacodynamics of 17-demethoxy 17- (2-dimethylamino) ethyl]amino] geldanamycin (17DMAG, NS C 707545) in C.B-17 SCID mice bearing MDA-MB-231 human breast cancer xenografts. Cancer Chemother. Pharmacol. 2005, 55, 21-32.
47. Yano, M.; Naito, Z.; Tanaka, S.; Asano, G. Expression and roles of heat shock proteins in human breast cancer. Jpn. J. Cancer Res. 1996, 87, 908-915.
48. Banerji, U.; Walton, M.; Raynaud, F.; Grimshaw, R.; Kelland, L.; Valenti, M.; Judson, I.; Workman, P. Pharmacokinetic-pharmacodynamic relationships for the heat shock protein 90 molecular chaperone inhibitor 17-allylamino, 17-demethoxygeldanamycin in human ovarian cancer xenograft models. Clin. Cancer Res. 2005, 11, 7023-7032.
49. Smith-Jones, P. M.; Solit, D. B.; Akhurst, T.; Afroze, F.; Rosen, N.; Larson, S. M. Imaging the pharmacodynamics of HER2 degradation in response to Hsp90 inhibitors. Nat. Biotechnol. 2004, 22, 701-706.
50. Smith-Jones, P. M.; Solit, D. B. Generation of DOTA-conjugated antibody fragments for radioimmunoimaging. Methods Enzymol. 2004, 386, 262-275.
51. Modi, S.; Stopeck A.; Gordon, M. S.; Solit, D.; Bagatell, R.; Flores, S.; Cohen, J.; Block, H.; Cropp, G. F.; Rosen, N.; Johnson, R. G.; Hannah, A.; Hudis, C. A. Trastuzumab (T) and KOS-953 (17-AAG) is feasible and active in patients (pts) with metastatic breast cancer; Preliminary Results of a Phase 1/2 study. SABCS 2005, Abst 1095.
52. Dragovich, T.; Gordon, M.; Saif, W.; Erlichman, C.; Toft D.; Timony, G.; Burrows, F.; Padgett, C.; De Jager, R.; Von Hoff, D. Phase 1 Study of CNF1010 (lipid formulation of 17-(allylamino)-17-demethoxygeldanamycin: 17-AAG). Clin. Can. Res. 2005, 11, 9117s.
53. Biamonte, M. A.; Shi, J.; Hong, K.; Hurst, D. C.; Zhang, L.; Fan, J.; Busch, D. J.; Karjian, P. L.; Maldonado, A. A.; Sensintaffar, J. L.; Yang, Y. C.; Kamal, A.; Lough, R. E.; Lundgren, K.; Burrows, F. J.; Timony, G. A.; Boehm, M. F.; Kasibhatla, S. R. Orally active purine-based inhibitors of the heat shock protein 90. J. Med. Chem. 2006, 49, 817-828.
54. Hollingshead, M.; Alley, M.; Burger, A. M.; Borgel, S.; Pacula-Cox, C.; Fiebig, H. H.; Sausville, E. A. In vivo antitumor efficacy of 17-DMAG (17-dimethylaminoethylamino-17-demethoxygeldanamycin hydrochloride), a water-soluble geldanamycin derivative. Cancer Chemother. Pharmacol. 2005.
55. Chiosis, G.; Timaul, M. N.; Lucas, B.; Munster, P. N.; Zheng, F. F.; Sepp-Lorenzino, L.; Rosen, N. A small molecule designed to bind to the adenine nucleotide pocket of Hsp90 causes Her2 degradation and the growth arrest and differentiation of breast cancer cells. Chem. Biol. 2001, 8, 289-299.
56. Llauger, L.; He, H.; Kim, J.; Aguirre, J.; Rosen, N.; Peters, U.; Davies, P.; Chiosis, G. Evaluation of 8-arylsulfanyl, 8-arylsulfoxyl, and 8-arylsulfonyl adenine derivatives as inhibitors of the heat shock protein 90. J. Med. Chem. 2005, 48, 2892-2905.
57. He, H.; Zatorska, D.; Kim, J.; Aguirre, J.; Llauger, L.; She, Y.; Wu, N.; Immormino, R. M.; Gewirth, D. T.; Chiosis, G. Identification of potent water soluble purine-scaffold inhibitors of the heat shock protein 90. J. Med. Chem. 2006, 49, 381-390.
58. Zhang, H.; Neely, L.; Yang, Y.-C.; Burrows, F. Influence of Multidrug Resistance Proteins on the Antitumor Activity of Natural and Synthetic Hsp90 Inhibitors. Clin. Can. Res. 2005, 11, 9108-9109s.
59. Cheung, K. M.; Matthews, T. P.; James, K.; Rowlands, M. G.; Boxall, K. J.; Sharp, S. Y.; Maloney, A.; Roe, S. M.; Prodromou, C.; Pearl, L. H.; Aherne, G. W.; McDonald, E.; Workman, P. The identification, synthesis, protein crystal structure and in vitro biochemical evaluation of a new 3,4-diarylpyrazole class of Hsp90 inhibitors. Bioorg. Med. Chem. Lett. 2005, 15, 3338-3343.
60. Marcu, M. G.; Schulte, T. W.; Neckers, L. Novobiocin and related coumarins and depletion of heat shock protein 90-dependent signaling proteins. J. Natl. Cancer Inst. 2000, 92, 242-248.
61. Marcu, M. G.; Chadli, A.; Bouhouche, I.; Catelli, M.; Neckers, L. M. The heat shock protein 90 antagonist novobiocin interacts with a previously unrecognized ATP-binding domain in the carboxyl terminus of the chaperone. J. Biol. Chem. 2000, 275, 37181-37186.
62. Soti, C.; Racz, A.; Csermely, P. A Nucleotide-dependent molecular switch controls ATP binding at the C-terminal domain of Hsp90. N-terminal nucleotide binding unmasks a C-terminal binding pocket. J. Biol. Chem. 2002, 277, 7066-7075.
63. Rosenhagen, M. C.; Soti, C.; Schmidt, U.; Wochnik, G. M.; Hartl, F. U.; Holsboer, F.; Young, J. C.; Rein, T. The heat shock protein 90-targeting drug cisplatin selectively inhibits steroid receptor activation. Mol. Endocrinol. 2003, 17, 1991-2001.
64. Bali, P.; Pranpat, M.; Bradner, J.; Balasis, M.; Fiskus, W.; Guo, F.; Rocha, K.; Kumaraswamy, S.; Boyapalle, S.; Atadja, P.; Seto, E.; Bhalla, K. 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.
65. Kovacs, J. J.; Murphy, P. J.; Gaillard, S.; Zhao, X.; Wu, J. T.; Nicchitta, C. V.; Yoshida, M.; Toft, D. O.; Pratt, W. B.; Yao, T. P. HDAC6 regulates Hsp90 acetylation and chaperone-dependent activation of glucocorticoid receptor. Mol. Cell 2005, 18, 601-607.
66. Yu, X.; Guo, Z. S.; Marcu, M. G.; Neckers, L.; Nguyen, D. M.; Chen, G. A.; Schrump, D. S. Modulation of p53, ErbB1, ErbB2, and Raf-1 expression in lung cancer cells by depsipeptide FR901228. J. Natl. Cancer Inst. 2002, 94, 504-513.
67. Chen, L.; Meng, S.; Wang, H.; Bali, P.; Bai, W.; Li, B.; Atadja, P.; Bhalla, K. N.; Wu, J. Chemical ablation of androgen receptor in prostate cancer cells by the histone deacetylase inhibitor LAQ824. Mol. Cancer Ther. 2005, 4, 1311-1319.
68. Bali, P.; Pranpat, M.; Swaby, R.; Fiskus, W.; Yamaguchi, H.; Balasis, M.; Rocha, K.; Wang, H. G.; Richon, V.; Bhalla, K. Activity of suberoylanilide hydroxamic Acid against human breast cancer cells with amplification of her-2. Clin. Cancer Res. 2005, 11, 6382-6389.
69. George, P.; Bali, P.; Annavarapu, S.; Scuto, A.; Fiskus, W.; Guo, F.; Sigua, C.; Sondarva, G.; Moscinski, L.; Atadja, P.; Bhalla, K. 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.
70. Stepanova, L.; Leng, X.; Parker, S. B.; Harper, J. W. Mammalian p50Cdc37 is a protein kinase-targeting subunit of Hsp90 that binds and stabilizes Cdk4. Genes Dev. 1996, 10, 1491-1502.
71. Ochel, H. J.; Schulte, T. W.; Nguyen, P.; Trepel, J.; Neckers, L. The benzoquinone ansamycin geldanamycin stimulates proteolytic degradation of focal adhesion kinase. Mol. Genet. Metab. 1999, 66, 24-30.
72. Arlanter, S. J.; Eapen, A. K.; Vroman, B. T.; McDonald, R. J.; Toft D. O.; Karnitz, L. M. Hsp90 inhibition depletes Chk1 and sensitizes tumor cells to replication stress. J. Biol. Chem. 2003, 278, 52572-52577.
73. de Carcer, G. Heat shock protein 90 regulates the metaphase-anaphase transition in a polo-like kinase-dependent manner. Cancer Res. 2004, 64, 5106-5112.
74. Yao, Q.; Nishiuchi, R.; Li, Q.; Kumar, A. R.; Hudson, W. A.; Kersey, J. H. FLT3 expressing leukemias are selectively sensitive to inhibitors of the molecular chaperone heat shock protein 90 through destabilization of signal transduction-associated kinases. Clin. Cancer Res. 2003, 9, 4483-4493.
75. Castro, J. E.; Prada, C. E.; Loria, O.; Kamal, A.; Chen, L.; Burrows, F. J.; Kipps, T. J. ZAP-70 is a novel conditional heat shock protein 90 (Hsp90) client: inhibition of Hsp90 leads to ZAP-70 degradation, apoptosis, and impaired signaling in chronic lymphocytic leukemia. Blood 2005, 106, 2506-2512.
76. Xu, Y.; Lindquist, S. Heat-shock protein hsp90 governs the activity of pp60v-src kinase. Proc. Natl. Acad. Sci. USA 1993. 90, 7074-7078.
77. 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, 1799-1804.
78. Fumo, G.; Akin, C.; Metcalfe, D. D.; Neckers, L. 17-Allylamino-17-demethoxygeldanamycin (17-AAG) is effective in down-regulating mutated, constitutively activated KIT protein in human mast cells. Blood 2004, 103, 1078-1084.
79. Yu, W.; Rao, Q.; Wang, M.; Tian, Z.; Lin, D.; Liu, X.; Wang, J. The Hsp90 inhibitor 17-allylamide-17-demethoxygeldanamycin induces apoptosis and differentiation of Kasumi-1 harboring the Asn822Lys KIT mutation and down-regulates KIT protein level. Leuk. Res. 2005, 30, 575-82.
80. Bonvini, P.; Dalla Rosa, H.; Vignes, N.; Rosolen, A. Ubiquitination and proteasomal degradation of nucleophosmin-anaplastic lymphoma kinase induced by 17-allylamino-demethoxygel-danamycin: role of the co-chaperone carboxyl heat shock protein 70-interacting protein. Cancer Res. 2004, 64, 3256-3264.
81. Beliakoff, J.; Bagatell, R.; Paine-Murrieta, G.; Taylor, C. W.; Lykkesfeldt, A. E.; Whitesell, L. Hormone-refractory breast cancer remains sensitive to the antitumor activity of heat shock protein 90 inhibitors. Clin. Cancer Res. 2003, 9. 4961-4971.
82. Villa, R.; Folini, M.; Ports, C. D.; Valentini, A.; Pennati, M.; Daidone, M. G.; Zaffaroni, N. Inhibition of telomerase activity by geldanamycin and 17-allylamino, 17-demethoxygeldanamycin in human melanoma cells. Carcinogenesis 2003, 24, 851-859.
83. Whitesell, L.; Sutphin, P. D.; Pulcini, E. J.; Martinez, J. D.; Cook, P. H. The physical association of multiple molecular chaperone proteins with mutant p53 is altered by geldanamycin, an hsp90-binding agent. Mol. Cell Biol. 1998, 18, 1517-1524.
84. Isaacs, J. S.; Jung, Y. J.; Mimnaugh, E. G.; Martinez, A.; Cuttitta, F.; Neckers, L. M. Hsp90 regulates a von Hippel Lindau-independent hypoxia-inducible factor-1 alpha-degradative pathway. J. Biol. Chem. 2002, 277, 29936-29944.
85. Garcia-Cardena, G.; Fan, R.; Shah, V.; Sorrentino, R.; Cirino, G.; Papapetropoulos, A.; Sessa, W. C. Dynamic activation of endothelial nitric oxide synthase by Hsp90. Nature 1998, 392, 821-824.
86. Pandey, P.; Saleh, A.; Nakazawa, A.; Kumar, S.; Srinivasula, S. M.; Kumar, V.; Weichselbaum, R.; Nalin, C.; Alnemri, E. S.; Kufe, D.; Kharbanda, S. Negative regulation of cytochrome c-mediated oligomerization of Apaf-1 and activation of procaspase-9 by heat shock protein 90. EMBO J. 2000, 19, 4310-4322.
87. Peng, Y.; Chen, L.; Li, C.; Lu, W.; Chen, J. Inhibition of MDM2 by hsp90 contributes to mutant p53 stabilization. J. Biol. Chem. 2001, 276, 40583-40590.
88. Fortugno, P.; Beltrami, E.; Plescia, J.; Fontana, J.; Pradhan, D.; Marchisio, P. C.; Sessa, W. C.; Altieri, D. C. Regulation of survivin function by Hsp90. Proc. Natl. Acad. Sci. USA 2003, 100, 13791-13796.
89. Nguyen, D. M.; Lorang, D.; Chen, G. A.; Stewart, J. H. t.; Tabibi, E.; Schrump, D. S. Enhancement of paclitaxel-mediated cytotoxicity in lung cancer cells by 17-allylamino geldanamycin: in vitro and in vivo analysis. Ann. Thorac. Surg. 2001, 72, 371-378; discussion 378-379.
90. Rakitina, T. V.; Vasilevskaya, I. A.; O'Dwyer, P. J. Additive interaction of oxaliplatin and 17-allylamino-17-demethoxygeldanamycin in colon cancer cell lines results from inhibition of nuclear factor kappaB signaling. Cancer Res. 2003, 63, 8600-8605.
91. Mesa, R. A.; Loegering, D.; Powell, H. L.; Flatten, K.; Arlander, S. J.; Dai, N. T.; Heldebrant, M. P.; Vroman, B. T.; Smith, B. D.; Karp, J. E.; Eyck, C. J.; Erlichman, C.; Kaufmann, S. H.; Karnitz, L. M. Heat shock protein 90 inhibition sensitizes acute myelogenous leukemia cells to cytarabine. Blood 2005, 106, 318-327.
92. Vasilevskaya, I. A.; Rakitina, T. V.; O'Dwyer, P. J. Quantitative effects on c-Jun N-terminal protein kinase signaling determine synergistic interaction of cisplatin and 17-allylamino-17-demethoxygeldanamycin in colon cancer cell lines. Mol. Pharmacol. 2004, 65, 235-243.
93. Radujkovic, A.; Schad, M.; Topaly, J.; Veldwijk, M. R.; Laufs, S.; Schultheis, B. S.; Jauch, A.; Melo, J. V.; Fruehauf, S.; Zeller, W. J. 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, 1198-1206.
94. Mimnaugh, E. G.; Xu, W.; Vos, M.; Yuan, X.; Isaacs, J. S.; Bisht, K. S.; 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. 551-566.
95. Rahmani, M.; Yu, C.; Dui, Y.; Reese, E.; Ahmed, W.; Dent; P.; Grant, S. Coadministration of the heat shock protein 90 antagonist 17-allylammo- 17-demethoxygeldanamycin with suberoylanilide hydroxamic acid or sodium butyrate synergistically induces apoptosis in human leukemia cells. Cancer Res. 2003, 63, 8420-8427.
96. Rahmani, M.; Reese, E.; Dai, Y.; Bauer, C.; Kramer, L. B.; Huang, M.; Jove, R.; Dent; P.; Grant, S. Cotreatment with suberanoylanilide hydroxamic acid and 17-allylamino 17-demethoxygeldanamycin synergistically induces apoptosis in Bcr-Abl+ Cells sensitive and resistant to STI571 (imatinib mesylate) in association with down-regulation of Bcr-Abl, abrogation of signal transducer and activator of transcription 5 activity, and Bax conformational change. Mol. Pharmacol. 2005, 67, 1166-1176.
97. Jia, W.; Yu, C.; Rahmani, M.; Krystal, G.; Sausville, E. A.; Dent, P.; Grant, S. Synergistic antileukemic interactions between 17-AAG and UCN-01 involve interruption of RAF/MEK- and AKT-related pathways. Blood 2003, 102, 1824-1832.
98. Premkumar, D. R.; Arnold, B.; Jane, E. P.; Pollack, I. F. Synergistic interaction between 17-AAG and phosphatidylinositol 3-kinase inhibition in human malignant glioma cells. Mol. Carcinog. 2006, 45, 47-59.
99. Yao, Q.; Nishiuchi, R.; Kitamura, T.; Kersey, J. H. Human leukemias with mutated FLT3 kinase are synergistically sensitive to FLT3 and Hsp90 inhibitors: the key role of the STAT5 signal transduction pathway. Leukemia 2005, 19, 1605-1612.
100. George, P.; Bali, P.; Cohen, P.; Tao, J.; Guo, F.; Sigua, C.; Vishvanath, A.; Fiskus, W.; Scuto, A.; Annavarapu, S.; Moscinski, L.; Bhalla, K. Cotreatment with 17-allylamino-demethoxygeldanamycin and FLT-3 kinase inhibitor PKC412 is highly effective against human acute myelogenous leukemia cells with mutant FLT-3. Cancer Res. 2004, 64, 3645-3652.
101. Russell, J. S.; Burgan, W.; Oswald, K. A.; Camphausen, K.; Tofilon, P. J. Enhanced cell killing induced by the combination of radiation and the heat shock protein 90 inhibitor 17-allylamino-17-demethoxygeldanamycin: a multitarget approach to radiosensitization. Clin. Cancer Res. 2003, 9, 3749-3755.
102. Bisht, K. S.; Bradbury, C. M.; Mattson, D.; Kaushal, A.; Sowers, A.; Markovina, S.; Ortiz, K. L.; Sieck, L. K.; Isaacs, J. S.; Brechbiel, M. W.; Mitchell, J. B.; Neckers, L. M.; Gius, D. Geldanamycin and 17-allylamino-17-demethoxygeldanamycin potentiate the in vitro and in vivo radiation response of cervical tumor cells via the heat shock protein 90-mediated intracellular signaling and cytotoxicity. Cancer Res. 2003, 63, 8984-8995.
103. Zou, J.; Guo, Y.; Guettouche, T.; Smith, D. F.; Voellmy, R. Repression of heat shock transcription factor HSF1 activation by HSP90 (HSP90 complex) that forms a stress-sensitive complex with HSF1. Cell 1998, 94, 471-480.