Synta Pharmaceuticals has developed a new Hsp90 inhibitor they’ve named Ganetespib (aka STA-9090).  Hsp90, a heat shock protein and chaperone, is found in many cells of the body and is a necessary player for cellular growth, proliferation and survival of cancer cells.  Specifically, many oncogenic proteins are clients of Hsp90 and appear to be degraded when deprived of this association with Hsp90.  By inhibiting Hsp90, Ganetespib is currently being tested as a therapy for several cancers in over 20 clinical trials.

One such study performed by the Dana-Farber Institute (in association with the Brigham and Women’s Hospital, Harvard Medical School and the Broad Institute of MIT and Harvard) has concluded that Ganetespib has great potential as a therapy against non-small cell lung cancer, including the common EGFR and ERBB2 mutations, both in vivo and in vitro.  In the article “Ganetespib (STA-9090), a Nongeldanamycin HSP90 Inhibitor, Has Potent Antitumor Activity in In Vitro and In Vivo Models of Non–Small Cell Lung Cancer (NSCLC)”, these scientists have determined that Ganetespib is indeed more effective than the previous generation of Hsp90 inhibitors; notably the Geldanamycin 17-AAG family.

Experiments were conducted to compare the effects of Ganetespib and Geldanamycin 17-AAG on Hsp90 inhibition.  It made use of biochemical assays, cell lines and xenographs for the comparison.  As a method for this evaluation, the disruption of Hsp90 binding to p23 (a co-chaperone) was used to establish the activity of the two inhibitors.  It was shown that far smaller amounts of the Ganetespib was necessary to achieve the same result as much larger amounts of 17-AAG; pointing to its greater efficacy.  It also concluded that one-time administrations of the inhibitor would not achieve lasting results, whereas weekly or daily dosage showed sustained effects on the NSCLC cells.

The original research paper was published in: Clinical Cancer Research, July 17, 2012 (online):

Ganetespib (STA-9090), a Nongeldanamycin HSP90 Inhibitor, Has Potent Antitumor Activity in In Vitro and In Vivo Models of Non–Small Cell Lung Cancer.