Targeted inhibition of Hsp90 by ganetespib is effective across a broad spectrum of breast cancer subtypes.

ABSTRACT: Heat shock protein 90 (Hsp90) is a molecular chaperone essential for the stability and function of multiple cellular client proteins, a number of which have been implicated in the pathogenesis of breast cancer. Here we undertook a comprehensive evaluation of the activity of ganetespib, a selective Hsp90 inhibitor, in this malignancy. With low nanomolar potency, ganetespib reduced cell viability in a panel of hormone receptor-positive, HER2-overexpressing, triple-negative and inflammatory breast cancer cell lines in vitro. Ganetespib treatment induced a rapid and sustained destabilization of multiple client proteins and oncogenic signaling pathways and even brief exposure was sufficient to induce and maintain suppression of HER2 levels in cells driven by this receptor. Indeed, HER2-overexpr

SUBMITTER: Friedland JC 

PROVIDER: S-EPMC3913847 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature