Consecutive Day HSP90 Inhibitor Administration Improves Efficacy in Murine Models of KIT-Driven Malignancies and Canine Mast Cell Tumors.

ABSTRACT:

Purpose

STA-1474, prodrug of the heat shock protein 90 inhibitor (HSP90i) ganetespib, previously demonstrated activity in canine preclinical models of cancer; interestingly, prolonged infusions were associated with improved biologic activity. The purpose of this study was to identify the ideal treatment schedule for HSP90i in preclinical models of KIT-driven malignancies and in dogs with spontaneous mast cell tumors (MCT), where KIT is a known driver.

Experimental design

In vitro and murine xenograft experiments and clinical studies in dogs with MCTs were used to define the effects of HSP90i-dosing regimen on client protein downregulation and antitumor activity.

Results

Continuous HSP90 inhibition led to durable destabilization of client proteins in vitro

SUBMITTER: London CA 

PROVIDER: S-EPMC6696991 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature