–Blocks HER2, ER, PR, AKT and MAPK signaling pathways–
–Active in broad range of in vitro, in vivo models–
–Shows synergy with lapatinib, doxorubicin, and PI3K/mTOR inhibition–
“These results demonstrating that ganetespib potently inhibits key
signaling pathways involved in the growth and proliferation of multiple
forms of breast cancer are encouraging, and supportive of the results
presented earlier at this meeting showing single-agent, anti-tumor
activity in patients with breast cancer who have progressed on or failed
to respond to multiple prior therapies,” said
Synta plans to initiate a company-sponsored trial for ganetespib in both
HER2-positive and triple-negative breast cancer in early 2012. In
In preclinical studies, ganetespib inhibits key signaling pathways in multiple subtypes of breast cancer. In hormone positive breast cancer, ganetespib induces the degradation of estrogen and progesterone receptor as well as Cyclin D1. In HER2 amplified breast cancer, ganetespib displays durable suppression of HER2 and its downstream signaling partners. In triple-negative and inflammatory breast cancers, ganetespib strongly inhibits AKT and MAPK signaling resulting in the upregulation of key apoptotic markers. In addition, ganetespib effectively suppresses STAT3 signaling, which may be particularly relevant in light of recent studies highlighting the frequency of activated STAT3 in triple negative breast cancer (Marotta et al., JCI, 2011).
In preclinical studies of combination treatments, ganetespib was shown to sensitize breast cancer cells to standard-of-care anticancer agents such as doxorubicin and targeted agents such as Tykerb® (lapatinib), as well as PI3K/mTOR inhibition, a class with emerging promise in breast cancer.
Ganetespib is the most advanced of the next-generation, synthetic Hsp90
inhibitors with over 450 patients treated to date; 20 trials completed,
ongoing, or initiating; and the Phase 2b/3 GALAXY Trial™ in second-line
non-small cell lung cancer (NSCLC) active in the U.S. and
Ganetespib has shown anti-tumor activity in heavily pretreated patients with lung cancer, breast cancer, and other tumor types and has been well tolerated with no evidence of severe liver or common ocular toxicities seen with other Hsp90 inhibitors. The most common adverse event seen to date has been diarrhea, which has been manageable with standard supportive care.
Interim results from the 240-patient Phase 2b portion of the GALAXY Trial™ are expected in first half of 2012, and final data in the second half of the year. Interim results from trials in ALK+ NSCLC, HER2+ breast cancer, and triple-negative breast cancer are also expected in the second half of 2012.
Information on clinical trials with ganetespib can be found at www.clinicaltrials.gov.
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 ALK, AKT, BCR-ABL, BRAF, KIT, MET, EGFR, FLT3, HER2, PDGFRA, 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.
Safe Harbor Statement
This media release may contain forward-looking statements about
Synta Pharmaceuticals Corp.
Rob Kloppenburg, 781-541-7125