Synta Announces Publications Demonstrating Ganetespib Activity in Triple-Negative Breast Cancer Models
The results demonstrate the ability of ganetespib to down-regulate a
number of key proteins involved in tumor growth and metastasis. Results
by Synta collaborators at
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“Ganetespib blocks HIF-1 activity and inhibits tumor growth,
vascularization, stem cell maintenance, invasion, and metastasis in
orthotopic mouse models of triple-negative breast cancer” by
Lisha Xiang ,Daniele M. Gilkes ,Pallavi Chaturvedi ,Weibo Luo ,Hongxia Hu ,Naoharu Takano , Houjie Liang, andGregg L. Semenza ,Journal of Molecular Medicine -
“Preclinical activity profile and therapeutic efficacy of the
Hsp90 inhibitor ganetespib in triple-negative breast cancer” by
David A. Proia ,Chaohua Zhang ,Manuel Sequeira ,John-Paul Jimenez ,Suqin He ,Neil L. Spector ,Geoffrey I. Shapiro ,Sara Tolaney ,Masazumi Nagai ,Jaime Acquaviva ,Donald L. Smith ,Jim Sang ,Richard C. Bates , andIman El-Hariry ,Clinical Cancer Research
A particularly sensitive protein to ganetespib treatment is HIF-1alpha, a major regulator of multiple tumor growth properties, including angiogenesis (tumor blood vessel development), metastasis (cancer spread), metabolism, cancer stem cell maintenance, and invasion. The results demonstrate that inhibition of a wide collection of protein targets, including HIF-1alpha, correlate with potent effects on TNBC tumor cell viability and metastasis when ganetespib is administered as monotherapy or when combined with routinely used chemotherapeutics for treatment of TNBC, including doxorubicin, paclitaxel, and docetaxel.
As previously reported by Synta, clinical activity was also observed along with a favorable toxicity profile in two TNBC patients treated with ganetespib monotherapy in the company-sponsored ENCHANT-1 Phase 2 trial.
References for both publications are available on the
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, and 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 trials in lung cancer, breast cancer, and other tumor
types. The most common adverse event seen to date has been transient,
mild or moderate diarrhea, which has been manageable with standard
supportive care. Information on these trials can be found at www.clinicaltrials.gov.
Ganetespib has received Fast Track designation from
About the ENCHANT-1 Clinical Trial
ENCHANT-1 is a proof-of-concept, ”window-of-opportunity” trial designed to evaluate single-agent ganetespib safety and clinical activity in locally advanced or first line metastatic HER2-positive and triple-negative breast cancer. The trial will also evaluate the combination of ganetespib with paclitaxel. More information about this trial can be found at www.clinicaltrials.gov (NCT01677455)
About Breast Cancer
Breast cancer is the most frequent cancer in women, accounting for
458,000 deaths worldwide in 2008, according to the
About
Source:
Synta Pharmaceuticals Corp.
George Farmer, 781-541-7213
[email protected]
or
Argot
Partners
Andrea Rabney, 212-600-1494
[email protected]