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Heat shock protein 90 inhibitors in the treatment of cancer: current status and future directions

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  • Zuehlke A, Johnson JL. Hsp90 and co-chaperones twist the functions of diverse client proteins. Biopolymers 2010;93(3):211-17
  • Workman P, Burrows F, Neckers L, et al. Drugging the cancer chaperone HSP90: combinatorial therapeutic exploitation of oncogene addiction and tumor stress. Ann N Y Acad Sci 2007;1113:202-16
  • Patel HJ, Modi S, Chiosis G, et al. Advances in the discovery and development of heat-shock protein 90 inhibitors for cancer treatment. Expert Opin Drug Discov 2011;6(5):559-87
  • Whitesell L, Lindquist SL. HSP90 and the chaperoning of cancer. Nat Rev Cancer 2005;5(10):761-72
  • Neckers L, Schulte TW, Mimnaugh E. Geldanamycin as a potential anti-cancer agent: its molecular target and biochemical activity. Invest New Drugs 1999;17(4):361-73
  • Sharma SV, Agatsuma T, Nakano H. Targeting of the protein chaperone, HSP90, by the transformation suppressing agent, radicicol. Oncogene 1998;16(20):2639-45
  • Schulte TW, Neckers LM. The benzoquinone ansamycin 17-allylamino-17-demethoxy geldanamycin binds to HSP90 and shares important biologic activities with geldanamycin. Cancer Chemother Pharmacol 1998;42(4):273-9
  • 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(18):4152-61
  • 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(6):1078-87
  • 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(9):1885-93
  • Jhaveri K, Taldone T, Modi S, et al. Advances in the clinical development of heat shock protein 90 (Hsp90) inhibitors in cancers. Biochim Biophys Acta 2012;1823(3):742-55
  • Heath EI, Hillman DW, Vaishampayan U, et al. A phase II trial of 17-allylamino-17-demethoxy geldanamycin in patients with hormone-refractory metastatic prostate cancer. Clin Cancer Res 2008;14(23):7940-6
  • Solit DB, Osman I, Polsky D, et al. Phase II trial of 17-allylamino-17-demethoxygeldanamycin in patients with metastatic melanoma. Clin Cancer Res 2008;14(24):8302-7
  • Ronnen EA, Kondagunta GV, Ishill N, et al. A phase II trial of 17-(Allylamino)-17-demethoxy geldanamycin in patients with papillary and clear cell renal cell carcinoma. Invest New Drugs 2006;24(6):543-6
  • Pacey S, Gore M, Chao D, et al. A Phase II trial of 17-allylamino, 17-demethoxygeldanamycin (17-AAG, tanespimycin) in patients with metastatic melanoma. Invest New Drugs 2012;30(1):341-9
  • Modi S, Stopeck A, Linden H, et al. HSP90 inhibition is effective in breast cancer: a phase II trial of tanespimycin (17-AAG) plus trastuzumab in patients with HER2-positive metastatic breast cancer progressing on trastuzumab. Clin Cancer Res 2011;17(15):5132-9
  • Richardson PG, Chanan-Khan AA, Lonial S, et al. Tanespimycin and bortezomib combination treatment in patients with relapsed or relapsed and refractory multiple myeloma: results of a phase 1/2 study. Br J Haematol 2011;153(6):729-40
  • PressRelease. Bristol-Myers Squibb Halts Development of Tanespimycin. 2008. Available from: http://www.myelomabeacon.com/news/2010/07/22/tanespimycin-development-halted/ [Last Accessed 8 January 2014]
  • Neckers L, Workman P. Hsp90 molecular chaperone inhibitors: are we there yet? Clin Cancer Res 2012;18(1):64-76
  • Tian ZQ, Liu Y, Zhang D, et al. Synthesis and biological activities of novel 17-aminogeldanamycin derivatives. Bioorg Med Chem 2004;12(20):5317-29
  • Hollingshead M, Alley M, Burger AM, et al. In vivo antitumor efficacy of 17-DMAG (17-dimethylaminoethylamino-17-demethoxygeldanamycin hydrochloride), a water-soluble geldanamycin derivative. Cancer Chemother Pharmacol 2005;56(2):115-25
  • Kummar S, Gutierrez ME, Gardner ER, et al. Phase I trial of 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), a heat shock protein inhibitor, administered twice weekly in patients with advanced malignancies. Eur J Cancer 2010;46(2):340-7
  • Lancet JE, Gojo I, Burton M, et al. Phase I study of the heat shock protein 90 inhibitor alvespimycin (KOS-1022, 17-DMAG) administered intravenously twice weekly to patients with acute myeloid leukemia. Leukemia 2010;24(4):699-705
  • Pacey S, Wilson RH, Walton M, et al. A phase I study of the heat shock protein 90 inhibitor alvespimycin (17-DMAG) given intravenously to patients with advanced solid tumors. Clin Cancer Res 2011;17(6):1561-70
  • Jhaveri K, Miller K, Rosen L, et al. A phase I dose-escalation trial of trastuzumab and alvespimycin hydrochloride (KOS-1022; 17 DMAG) in the treatment of advanced solid tumors. Clin Cancer Res 2012;18(18):5090-8
  • 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(46):17408-13
  • Siegel D, Jagannath S, Vesole DH, et al. A phase 1 study of IPI-504 (retaspimycin hydrochloride) in patients with relapsed or relapsed and refractory multiple myeloma. Leuk Lymphoma 2011;52(12):2308-15
  • Oh WK, Galsky MD, Stadler WM, et al. Multicenter phase II trial of the heat shock protein 90 inhibitor, retaspimycin hydrochloride (IPI-504), in patients with castration-resistant prostate cancer. Urology 2011;78(3):626-30
  • Sequist LV, Gettinger S, Senzer NN, et al. Activity of IPI-504, a novel heat-shock protein 90 inhibitor, in patients with molecularly defined non-small-cell lung cancer. J Clin Oncol 2010;28(33):4953-60
  • Wagner AJ, Morgan JA, Chugh R, et al. Inhibition of heat shock protein 90 (Hsp90) with the novel agent IPI-504 in metastatic GIST following failure of tyrosine kinase inhibitors (TKIs) or other sarcomas: clinical results from phase I trial. J Clin Oncol 2008;26:abstract 10503
  • Normant E, Paez G, West KA, et al. The Hsp90 inhibitor IPI-504 rapidly lowers EML4-ALK levels and induces tumor regression in ALK-driven NSCLC models. Oncogene 2011;30(22):2581-6
  • Sequist LV, Natale RB, Senzer NN, et al. Association between anaplastic lymphoma kinase rearrangements (rALK) and the clinical activity of IPI-504 (retaspimycin hydrochloride), a novel Hsp90 inhibitor, in patients with non-small cell lung cancer (NSCLC). J Clin Oncol 2010;28:abstract 7517
  • Demetri G, Le Cesne A, Von Mehren M, et al. Final results from a phase III study of IPI-504 (retaspimycin hydrochloride) versus placebo in patients (pts) with gastrointestinal stromal tumors (GIST) following failure of kinase inhibitor therapies. Gastrointestinal Cancers Symposium 2010;28:abstract-64
  • Modi S, Saura C, Henderson C, et al. A multicenter trial evaluating retaspimycin HCL (IPI-504) plus trastuzumab in patients with advanced or metastatic HER2-positive breast cancer. Breast Cancer Res Treat 2013;139(1):107-13
  • Rowlands MG, Newbatt YM, Prodromou C, et al. High-throughput screening assay for inhibitors of heat-shock protein 90 ATPase activity. Anal Biochem 2004;327(2):176-83
  • Cheung KM, Matthews TP, James K, et al. 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(14):3338-43
  • Jensen MR, Schoepfer J, Radimerski T, et al. NVP-AUY922: a small molecule HSP90 inhibitor with potent antitumor activity in preclinical breast cancer models. Breast Cancer Res 2008;10(2):R33
  • Samuel TA, Sessa C, Britten C, et al. AUY922, a novel HSP90 inhibitor: Final results of a first-in-human study in patients with advanced solid malignancies. J Clin Oncol 2010;28(Suppl):abstract 2528
  • Schroder C, Pederson JV, Chua S, et al. Use of biomarkers and imaging to evaluate the treatment effect of AUY922, an Hsp90 inhibitor, in patients with HER2+ or ER+ metastatic breast cancer. J Clin Oncol 2011;29(Suppl):abstract e11024
  • Garon EB, Moran T, Barlesi F, et al. Phase II study of the HSP90 inhibitor AUY922 in patients with previously treated, advanced non-small cell lung cancer (NSCLC). J Clin Oncol 2012;30(Suppl):abstract 7543
  • Johnson ML, Hart EM, Rademaker A, et al. A phase II study of HSP90 inhibitor AUY922 and erlotinib (E) for patients (pts) with EGFR-mutant lung cancer and acquired resistance (AR) to EGFR tyrosine kinase inhibitors (EGFR TKIs). J Clin Oncol 2013;31:abstract 8036
  • Kong A, Rea D, Ahmed S, et al. Phase IB/II study of the HSP90 inhibitor AUY922, in combination with trastuzumab, in patients with HER2 positive advanced breast cancer. J Clin Oncol 2012;30(Suppl):abstract 530
  • Murray CW, Carr MG, Callaghan O, et al. Fragment-based drug discovery applied to Hsp90. Discovery of two lead series with high ligand efficiency. J Med Chem 2010;53(16):5942-55
  • Woodhead AJ, Angove H, Carr MG, et al. Discovery of (2,4-dihydroxy-5-isopropylphenyl)-[5-(4-methylpiperazin-1-ylmethyl)-1,3-dihydroisoindol-2-yl]methanone (AT13387), a novel inhibitor of the molecular chaperone Hsp90 by fragment based drug design. J Med Chem 2010;53(16):5956-69
  • Mahadevan D, Rensvold DM, Kurtin SE, et al. First-in-human phase I study: Results of a second-generation non-ansamycin heat shock protein 90 (HSP90) inhibitor AT13387 in refractory solid tumors. J Clin Oncol 2012;30(Suppl):abstract 3028
  • Do KT, Speranza G, Chen AP, et al. Phase l study assessing a two-consecutive-day (QD x 2) dosing schedule of the HSP90 inhibitor, AT13387, in patients with advanced solid tumors. J Clin Oncol 2012;30:abstract 3087
  • Ying W, Du Z, Sun L, et al. Ganetespib, a unique triazolone-containing Hsp90 inhibitor, exhibits potent antitumor activity and a superior safety profile for cancer therapy. Mol Cancer Ther 2012;11(2):475-84
  • Choi HK, Lee K. Recent updates on the development of ganetespib as a Hsp90 inhibitor. Arch Pharm Res 2012;35(11):1855-9
  • Goldman JW, Raju RN, Gordon GA, et al. A first in human, safety, pharmacokinetics, and clinical activity phase I study of once weekly administration of the Hsp90 inhibitor ganetespib (STA-9090) in patients with solid malignancies. BMC Cancer 2013;13:152
  • Cho D, Heath EI, Cleary JM, et al. A phase I dose escalation study of the Hsp90 inhibitor ganetespib (STA-9090) administered twice weekly in patients with solid tumors: updated report. J Clin Oncol 2011;29:abstract 3051
  • Lancet JE, Smith BD, Bradley R, et al. A phase 1/2 study of the potent Hsp90 inhibitor STA-9090 administered once weekly in subjects with hematologic malignancies. Blood 2010;abstract 3294
  • Padmanabhan S, Kelly K, Heaney M, et al. A phase I study of the potent Hsp90 Inhibitor STA-9090 administered twice weekly in subjects with hematologic malignancies. Blood 2010;116:abstract 2898
  • Socinski MA, Goldman J, El-Hariry I, et al. A multicenter phase II study of ganetespib monotherapy in patients with genotypically defined advanced non–small cell lung cancer. Clin Cancer Res 2013;19(11):3068-77
  • Jhaveri K, Chandarlapaty S, Lake D, et al. A phase II open-label study of ganetespib, a novel heat shock protein 90 inhibitor for patients with metastatic breast cancer. Clin Breast Cancer 2013; Epub ahead of print
  • Demetri G, Heinrich MC, Chmielowski B, et al. An open-label phase II study of the Hsp90 inhibitor ganetespib (STA-9090) in patients (pts) with metastatic and/or unresectable GIST. J Clin Oncol 2011;29(Suppl):abstract 10011
  • Solit DB, Basso AD, Olshen AB, et al. Inhibition of heat shock protein 90 function down-regulates Akt kinase and sensitizes tumors to Taxol. Cancer Res 2003;63(9):2139-44
  • Jhaveri K, Modi S. Hsp90 inhibitors for cancer therapy and overcoming drug resistance. Adv Pharmacol 2012;65:471-517
  • Ramalingam S, Goss GD, Andric ZG, et al. A randomized study of ganetespib, a heat shock protein 90 inhibitor, in combination with docetaxel versus docetaxel alone for second-line therapy of lung adenocarcinoma (GALAXY-1). J Clin Oncol 2013;31(Suppl):abstract CRA8007
  • Proia DA, Zhang C, Sequeira M, et al. Preclinical activity profile and therapeutic efficacy of the Hsp90 inhibitor ganetespib in triple-negative breast cancer. Clin Cancer Res 2013;20(2):413-24
  • Cavenagh JD, Yong K, Byrne J, et al. The safety, pharmacokinetics and pharmacodynamics of KW-2478, a novel Hsp90 antagonist, in patients with B-cell malignancies: a first-in-man, phase I, multicentre, open-label, dose escalation study. Myeloma-Therapy Blood 2008;112:abstract 2777
  • Cavenagh J, Baylon HG, Caguioa PB, et al. A phase 1/2 study of KW-2478, an Hsp 90 inhibitor, in combination with bortezomib (BTZ) in patients (Pts) with relapsed/refractory (R/R) multiple myeloma (MM). Myeloma: Therapy, excluding Transplantation: Poster I Blood 2013;122:abstract 1967
  • Taldone T, Chiosis G. Purine-scaffold Hsp90 inhibitors. Curr Top Med Chem 2009;9(15):1436-46
  • Chene P. ATPases as drug targets: learning from their structure. Nat Rev Drug Discov 2002;1(9):665-73
  • Chiosis G, Timaul MN, Lucas B, et al. 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(3):289-99
  • Kasibhatla SR, Hong K, Biamonte MA, et al. Rationally designed high-affinity 2-amino-6-halopurine heat shock protein 90 inhibitors that exhibit potent antitumor activity. J Med Chem 2007;50(12):2767-78
  • Dickson MA, Okuno SH, Keohan ML, et al. Phase II study of the HSP90-inhibitor BIIB021 in gastrointestinal stromal tumors. Ann Oncol 2013;24(1):252-7
  • Modi S, Ismail-Khan R, Munster P, et al. Phase 1 dose-escalation study of the heat shock protein 90 inhibitor BIIB021 with trastuzumab in HER2+ metastatic breast cancer. Cancer Res 2010;70(24 Suppl 2):abstract P3-14-02
  • Mitchell P. Biogen Idec restructures, sharpens neurology focus. Nat Biotechnol 2011;29(1):7-8
  • He H, Zatorska D, Kim J, et al. Identification of potent water soluble purine-scaffold inhibitors of the heat shock protein 90. J Med Chem 2006;49(1):381-90
  • Dunphy M, Chiosis G, Beattie B, et al. Progress in first-in-human trial of Hsp90-targeted PET imaging in cancer patients. J Nucl Med 2013;54(Suppl 2):abstract 279
  • Gerecitano JF, Modi S, Gajria D, et al. Using 124I-PU-H71 PET imaging to predict intratumoral concentration in patients on a phase I trial of PU-H71. J Clin Oncol 2013;31(Suppl):abstract 11076
  • Kim SH, Bajji A, Tangallapally R, et al. Discovery of (2S)-1-[4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)sulfanyl]-9H-purin-9-yl}et hyl)piperidin -1-yl]-2-hydroxypropan-1-one (MPC-3100), a purine-based Hsp90 inhibitor. J Med Chem 2012;55(17):7480-501
  • Samlowski WE, Papadopoulos K, Olszanski AJ, et al. Phase 1 study of HSP90 inhibitor MPC-3100 in subjects with refractory or recurrent cancer. Molecular Targets and Cancer Therapeutics 2011;abstract A96
  • Bao R, Lai CJ, Qu H, et al. CUDC-305, a novel synthetic HSP90 inhibitor with unique pharmacologic properties for cancer therapy. Clin Cancer Res 2009;15(12):4046-57
  • Taldone T, Patel PD, Patel M, et al. Experimental and structural testing module to analyze paralogue-specificity and affinity in the Hsp90 inhibitors series. J Med Chem 2013;56(17):6803-18
  • Isambert N, Hollebecque A, Berge Y, et al. A phase I study of Debio 0932, an oral HSP90 inhibitor, in patients with solid tumors. J Clin Oncol 2012;30:abstract 3026
  • Fadden P, Huang KH, Veal JM, et al. Application of chemoproteomics to drug discovery: identification of a clinical candidate targeting Hsp90. Chem Biol 2010;17(7):686-94
  • Rajan A, Kelly RJ, Trepel JB, et al. A phase I study of PF-04929113 (SNX-5422), an orally bioavailable heat shock protein 90 inhibitor, in patients with refractory solid tumor malignancies and lymphomas. Clin Cancer Res 2011;17(21):6831-9
  • Esanex: out of stealth mode (barely). HSP90 Inhibitors Central. 2013. Available from: http://www.hsp90central.com/1/post/2013/01/esanex-out-of-stealth-mode-barely.html [Last Accessed 8 January 2014]
  • Menezes DL, Taverna P, Jensen MR, et al. The novel oral Hsp90 inhibitor NVP-HSP990 exhibits potent and broad-spectrum antitumor activities in vitro and in vivo. Mol Cancer Ther 2012;11(3):730-9
  • Mattos-Arruda LD, Siu LL, Cortes J, et al. Phase I dose-escalation, open-label study of HSP990 administered orally in adult patients with advanced solid malignancies. J Clin Oncol 2013;31(Suppl):abstract 2561^
  • Vernalis. Interim results for the six months ended 30 June 2012. 2012. Available from: http://www.vernalis.com/media-centre/latest-releases/2012-releases/642-interim-results-for-the-six-months-ended-30-june-2012 [Last Accessed 9 January 2014]
  • Bussenius J, Blazey CM, Aay N, et al. Discovery of XL888: a novel tropane-derived small molecule inhibitor of HSP90. Bioorg Med Chem Lett 2012;22(17):5396-404
  • Paraiso KH, Haarberg HE, Wood E, et al. The HSP90 inhibitor XL888 overcomes BRAF inhibitor resistance mediated through diverse mechanisms. Clin Cancer Res 2012;18(9):2502-14
  • Whitesell L, Lin NU. HSP90 as a platform for the assembly of more effective cancer chemotherapy. Biochim Biophys Acta 2012;1823(3):756-66
  • Ramalingam SS, Egorin MJ, Ramanathan RK, 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(11):3456-61
  • Goetz MP, Toft DO, Ames MM, et al. The Hsp90 chaperone complex as a novel target for cancer therapy. Ann Oncol 2003;14(8):1169-76
  • 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(1):21-32
  • Vilenchik M, Solit D, Basso A, et al. Targeting wide-range oncogenic transformation via PU24FCl, a specific inhibitor of tumor Hsp90. Chem Biol 2004;11(6):787-97
  • Kamal A, Thao L, Sensintaffar J, et al. A high-affinity conformation of Hsp90 confers tumour selectivity on Hsp90 inhibitors. Nature 2003;425(6956):407-10
  • Moulick K, Ahn JH, Zong H, et al. Affinity-based proteomics reveal cancer-specific networks coordinated by Hsp90. Nat Chem Biol 2011;7(11):818-26
  • Eiseman JL, Guo J, Ramanathan RK, et al. Evaluation of plasma insulin-like growth factor binding protein 2 and Her-2 extracellular domain as biomarkers for 17-allylamino-17-demethoxygeldanamycin treatment of adult patients with advanced solid tumors. Clin Cancer Res 2007;13(7):2121-7
  • Demetri GD, George S, Morgan JA, et al. Inhibition of the heat shock protein 90 (Hsp90) chaperone with the novel agent IPI-504 to overcome resistance to tyrosine kinase inhibitors (TKIs) in metastatic GIST: updated results of a phase I trial. J Clin Oncol 2007;25:abstract 10024
  • Holland JP, Caldas-Lopes E, Divilov V, et al. Measuring the pharmacodynamic effects of a novel Hsp90 inhibitor on HER2/neu expression in mice using Zr-DFO-trastuzumab. PLoS ONE 2010;5(1):e8859
  • Nagengast WB, de Korte MA, Oude Munnink TH, et al. 89Zr-bevacizumab PET of early antiangiogenic tumor response to treatment with HSP90 inhibitor NVP-AUY922. J Nucl Med 2010;51(5):761-7
  • Oude Munnink TH, Korte MA, Nagengast WB, et al. (89)Zr-trastuzumab PET visualises HER2 downregulation by the HSP90 inhibitor NVP-AUY922 in a human tumour xenograft. Eur J Cancer 2010;46(3):678-84
  • Jhaveri KL. Biomarkers that predict sensitivity to heat shock protein 90 inhibitors (HSP90i). J Clin Oncol 2012;30(Suppl):abstract 10618
  • Darby JF, Workman P. Chemical biology: many faces of a cancer-supporting protein. Nature 2011;478(7369):334-5
  • Beebe K, Mollapour M, Scroggins B, et al. Posttranslational modification and conformational state of heat shock protein 90 differentially affect binding of chemically diverse small molecule inhibitors. Oncotarget 2013;4(7):1065-74

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