Synta Pharmaceuticals Corp. (NASDAQ: SNTA) announced today publication of results from in vitro, in vivo, and translational clinical studies demonstrating the effect of ganetespib on the ability of tumors to grow new blood vessels (angiogenesis). The paper appeared in the July 10, 2013, online issue of Angiogenesis. Ganetespib, a selective inhibitor of the Hsp90 chaperone protein in development by Synta, is being evaluated in over 20 clinical trials for different types of cancer, including a pivotal Phase 3 trial in non-small cell lung cancer.
“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. Bassel El-Rayes, Director of the GI Oncology Translational Research Program, Winship Cancer Institute, Emory University and senior author of the paper. “The results published this week show that ganetespib may offer a third way to suppress angiogenesis: inhibiting the transcription factors that turn on production of VEGF and other pro-angiogenic factors. This is like turning off the faucet at the source, rather than trying to empty the sink once it is full.”
The publication describes results from preclinical studies and a rectal cancer clinical trial conducted at Emory University showing that ganetespib simultaneously downregulates the expression of many cellular proteins involved in new blood vessel formation, including VEGF, PDGFA, FGF2, Ang-1, Ang-2, TGFb1, HIF-1a, and STAT-3.
“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.”