Ganestespib (STA-9090) is a HSP90 inhibitor under development by Synta Pharmaceuticals Corp.
Mode of action: intravenously administered inhibitor of HSP90 and its client proteins (including KIT and PDGFRA)
Manufacturer website: http://www.syntapharma.com/
Information at Synta website: http://www.syntapharma.com/PrdHsp90.aspx
Definition from the NCI Drug Dictionary:
A synthetic small-molecule inhibitor of heat shock protein 90 (Hsp90) with potential antineoplastic activity. Hsp90 inhibitor STA-9090 binds to and inhibits Hsp90, resulting in the proteasomal degradation of oncogenic client proteins, the inhibition of cell proliferation and the elevation of heat shock protein 72 (Hsp72); it may inhibit the activity of multiple kinases, such as c-Kit, EGFR, and Bcr-Abl, which as client proteins depend on functional HsP90 for maintenance. Hsp90, a 90 kDa molecular chaperone upregulated in a variety of tumor cells, plays a key role in the conformational maturation, stability and function of "client" proteins within the cell, many of which are involved in signal transduction, cell cycle regulation and apoptosis, including kinases, transcription factors and hormone receptors. Hsp72 exhibits anti-apoptotic functions; its up-regulation may be used as a surrogate marker for Hsp90 inhibition.
Slide Set from Synta about STA-9090
Click here to view an Adobe pdf of a slide set from Synta explaining the actions of STA-9090, its results against GIST cell lines, and the clinical trials in which it is currently being tested.
Links to Effectiveness Data at the Synta website
Click here to view a page at the Synta website where you can link to numerous presentations about STA-9090, including data from the Phase I trials (now completed) presented at the 2010 ASCO meeting. Scroll down the page for the list of presentations.
Clinical Trials for GIST
In December 2009 Synta announced a new Phase II trial for GIST patients resistant to imatinib and sunitinib:
A Study Evaluating STA-9090 in Patients With Metastatic and/or Unresectable Gastrointestinal Stromal Tumor (GIST), NCT01039519 Click trial title for more information at clinicaltrials.gov
Link to read the Press Release describing this trial. Quoting from this press release:
"The non-randomized, open-label, multi-center Phase 2 study is designed to characterize the
efficacy and safety of STA-9090 in patients with metastatic or unresectable GIST following
failure of systemic treatment with imatinib (Gleevec®) and sunitinib (Sutent®). The trial will enroll
up to approximately 55 patients in a two-stage design. Patients will be stratified according to
whether or not they have been exposed to other Hsp90 inhibitors, and STA-9090 will be
administered as a single agent on a once-weekly intravenous dosing schedule. Patients
tolerating STA-9090 may continue on treatment until disease progression."
This Phase II trial is open at Dana-Farber Cancer Institute, with a few more sites to follow soon thereafter (Oregon Health Science University, Fox Chase Cancer Center and UCLA). Any patient who wants to contact Synta about the trial should telephone Robert Bradley at 781-541-7984 or e-mail him at firstname.lastname@example.org .
A Phase I trial of STA-9090 was begun in November 2007 at Dana-Farber Cancer Institute. The lead investigator is Geoffrey Shapiro, MD PhD. This trial uses a twice-per-week dosing schedule (trial NCT00688116).
A second Phase I trial with a once-per-week dosing schedule (trial NCT00687934) is ongoing but no longer recruiting.
A press release from manufacturer Synta Pharmaceuticals included these statements: "In preclinical studies, STA-9090 has shown the ability to inhibit multiple kinases with comparable potency to, and a broader activity profile than specific kinase inhibitors such as imatinib (Gleevec(R)), erlotinib (Tarceva(R)), and sunitinib (Sutent(R)). In addition, STA-9090 has shown potency 10 to 100 times greater than the geldanamycin family of Hsp90 inhibitors, as well as activity against a wider range of kinases. In in vivo models, STA-9090 has shown strong efficacy in a wide range of cancer types, including cancers resistant to Gleevec, Tarceva, and Sutent."
Press release at manufacturer's website: http://ir.syntapharma.com/releasedetail.cfm?ReleaseID=274813
Synta Pharmaceuticals Corp.
Rob Kloppenburg, 781-541-7125