Ganetespib in Breast Cancer (Clinical)
Gene expression and proteomic analysis to identify predictive
biomarkers of response in the ENCHANT-1 Trial (NCT01677455), a Phase 2
Proof of Concept study evaluation first-line ganetespib monotherapy in
women with metastatic HER2 positive or triple negative breast cancer
Abstract number: 1612
Authors: Petricoin, et al.
Ganetespib in Lung Cancer (Pre-Clinical)
The HSP90 inhibitor ganetespib potentiates effect of ionizing
radiation in human non-small cell lung cancer
Abstract number: 4894
Authors: Gomez-Casal, et al.
Low dose Ganetespib (STA-9090) enhances radiotherapy effects on lung
cancer cells by synergistically altering levels of cell cycle
Abstract number: 4902
Authors: Liu, et al.
Screening >60 human SCLC lines with approved and investigational
agents indicates complex patterns of response: Identification of HSP90
and HDACs as potential targets
Abstract number: 5450
Authors: Evans, et al.
Ganetespib in Other Cancers (Pre-Clinical)
Functional inhibition of HSP90 induces G0/G1 arrest and downregulates
thymidylate synthase in colorectal cancer
Abstract number: 1308
Authors: Nagaraju, et al.
The Hsp90 inhibitor ganetespib overcomes EGFR-based intratumoral
heterogeneity to block glioma proliferation
Abstract number: LB-140
Authors: Driscoll, et al.
The HSP90 inhibitor ganetespib synergizes with the MET kinase
inhibitor crizotinib in both crizotinib-sensitive and
crizotinib-resistant MET driven renal tumor models
Abstract number: 3722
Authors: Miyajima, et al.
HSP90 mediates tumor-associated matrix metalloproteinase 2 and
Cathepsin L protease activities in ovarian carcinoma
Abstract number: 3916
Authors: O’Brien, et al.
HSP90 as a therapeutic target in colorectal cancer
Abstract number: 4221
Authors: Nagaraju, et al.
A multimodality imaging end-point study of everolimus and ganetespib
in treatment of pancreatic cancer: A pre-clinical PET/MRI/MRS study
Abstract number: 4690
Authors: Lee, et al.
The Hsp90 inhibitor ganetespib is a potent chemosensitizer in
preclinical colorectal cancer models
Abstract number: 5108
Authors: He, et al.
Hsp90 inhibitor Drug Conjugates (HDC)
Hsp90 inhibitor drug conjugates (HDC): Construct design and
Abstract number: 1619
Authors: Ying, et al.
Hsp90 inhibitor drug conjugates (HDC): Novel tumor selective drug
delivery platform with superior anticancer activity
Abstract number: 2509
Authors: Chimmanamada, et al.
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 Hsp90 inhibitor Drug Conjugates (HDC)
HDCs are small-molecule drugs consisting of an Hsp90 inhibitor (targeting moiety) joined to an anti-cancer agent (payload) via a cleavable chemical linker optimized for controlled release of payload drug inside cancer cells. They exploit the preferential retention of Hsp90 inhibitors in tumors to selectively deliver anti-cancer payloads. HDCs represent a promising new therapeutic class with the potential to enhance the safety and efficacy of a wide range of small molecule anti-cancer drugs.
Synta has established proof of concept for HDC lead candidates in preclinical studies and has developed HDCs using a range of Hsp90 inhibitor moieties, cleavable linkers, and over 40 anti-cancer payloads. The latter include cytotoxic chemotherapeutics, kinase inhibitors, hormone therapies, immunomodulators, and epigenetic modifiers, creating the potential for next-generation compounds in each of these categories. Synta has filed worldwide patent applications that include comprehensive claims covering the HDC platform, compositions of matter, methods for identifying therapeutically effective compounds, and methods of use of such compounds against a wide range of diseases and conditions.
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Synta Pharmaceuticals Corp.
Steven Bernitz, 781-541-7250
Senior Vice President, Corporate Development
Andrea Rabney, 212-600-1494
Eliza Schleifstein, 917-763-8106