Synta Announces Publication of Clinical and Non-Clinical Results Demonstrating Unique Anti-angiogenic Effects of Ganetespib
– Results Suggest Targeting Hsp90 May Inhibit Angiogenesis without Tumor Rebound Effects Associated with VEGF-Targeted Anti-angiogenic Therapies –
– Support Rationale for Combining Ganetespib with Standard Anti-angiogenic Agents –
“To date two therapeutic strategies have been established for inhibiting
new tumor blood vessel formation: agents that bind directly to
vasculature growth factors (e.g., VEGF), or agents that bind to their
cellular receptors (e.g., VEGFR),” said Dr.
The publication describes results from preclinical studies and a rectal
cancer clinical trial conducted at
“Targeting angiogenesis with anti-VEGF therapies has demonstrated meaningful clinical benefit, but has also been associated with greater disease aggressiveness and metastasis from increased expression of VEGF-A and activation of HIF-1a in the hypoxic tumor,” said Dr. El-Rayes. “These studies show that the unique mechanism of action of ganetespib may provide a means to downregulate angiogenesis without upregulating HIF-1a activation and VEGF expression. These effects strongly support the rationale to combine ganetespib with standard anti-angiogenic agents.”
Previously presented results showed synergistic activity of ganetespib and the anti-angiogenic agent bevacizumab, an antibody targeting VEGF, in preclinical models of cancer.
About Ganetespib
Ganetespib, an investigational drug candidate, is a selective inhibitor of heat shock protein 90 (Hsp90), a molecular chaperone which controls the folding and activation of a number of client proteins that drive tumor development and progression. Many solid and hematologic tumors are dependent on Hsp90 client proteins including proteins involved in “oncogene addiction” (ALK, HER2, mutant BRAF and EGFR, androgen receptor, estrogen receptor, JAK2); proteins involved in resistance to chemotherapy and radiation therapy (ATR, BCL2, BRCA1/2, CDK1/4, CHK1, survivin, and WEE1); proteins involved in angiogenesis (HIF-1alpha, VEGFR, PDFGR, and VEGF); and proteins involved in metastasis (MET, RAF, AKT, MMPs, HIF-1alpha, and IGF-1R). In preclinical models, inhibition of Hsp90 by ganetespib results in the inactivation, destabilization, and eventual degradation of these cancer-promoting proteins. Ganetespib is being evaluated in over 20 clinical trials including trials in lung, breast, colorectal, and hematologic malignancies. Information on these trials can be found at www.clinicaltrials.gov.
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George
Farmer, 781-541-7213
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Andrea Rabney, 212-600-1494
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