Inhibition of mTOR enhances the activity of HSP90 inhibitors in part through cessation of heat shock protein synthesis
Abstract number: 1038
Authors: He, et al.
Ultra-deep sequencing of circulating free DNA to identify predictive, mutated HSP90 clients in the GALAXY Trial (NCT01348126): a randomized phase IIB/III study of ganetespib (STA-9090) in combination with docetaxel versus docetaxel alone in subjects with stage IIIb/IV NSCLC
Abstract number: 2012
Authors: Fennell, et al.
The importance of dose schedule with HSP90 inhibitors: Results from a Phase II study in dogs with mast cell tumors
Abstract number: 3369
Differential sensitivities to heat shock protein 90 (HSP90) inhibitors in anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) cells
Abstract number: 3272
Authors: Lee, et al.
Heat shock protein 90 functional inhibition regulates epithelial to mesenchymal transformation, invasion and migration via NF-kB and HIF-1α signaling in colorectal cancer
Abstract number: 2707
Authors: Ganji, et al.
Ganetespib is an inhibitor of heat shock protein 90 (Hsp90) that is structurally unrelated to first-generation, ansamycin-related Hsp90 inhibitors. In preclinical experiments, ganetespib has shown activity in multiple tumor models both as a single agent and in combination with certain widely used cancer agents. Company-sponsored clinical studies with ganetespib include 1) the randomized GALAXY-1 and GALAXY-2 trials evaluating ganetespib in combination with docetaxel as second-line treatment of non-small cell lung cancer (NSCLC), 2) the CHIARA Phase 2 trial evaluating ganetespib monotherapy in ALK+ NSCLC, and 3) the ENCHANT Phase 2 trial evaluating ganetespib as first-line treatment for HER2+ and triple-negative metastatic breast cancer. In addition, ganetespib is being evaluated in investigator-sponsored trials for treatment of a number of solid tumor and hematologic cancer indications. Information on these trials can be found at www.clinicaltrials.gov.
The safety profile of ganetespib has been favorable in over 700 patients treated to date in more than 20 clinical trials. Transient, mild or moderate diarrhea has been the most commonly reported adverse event.
Hsp90 is a molecular chaperone required for the proper folding and activation of many cancer-promoting proteins, and is recognized as a key facilitator of cancer cell growth and survival. Many of the “client proteins” of Hsp90 – such as AKT, ALK, BCR-ABL, BRAF, EGFR, FLT3, HER2, HIF-1alpha, KIT, MET, PDGFRA, and VEGFR – are the targets of clinically validated cancer drugs. In preclinical studies, inhibiting Hsp90 causes the degradation of multiple client proteins and leads to cancer cell death.
About the GALAXY Trials
The GALAXY (Ganetespib Assessment in Lung cAncer with docetaXel) program consists of two randomized trials comparing the combination of ganetespib and docetaxel versus docetaxel alone in patients with Stage IIIB/IV NSCLC who have received one prior systemic therapy: a 300-patient Phase 2b/3 trial (GALAXY-1) to determine the patient population most likely to derive benefit from ganetespib, and a 500-patient confirmatory Phase 3 trial (GALAXY-2). More information about the GALAXY trials can be found at www.clinicaltrials.gov (NCT01348126 and NCT01798485).
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