CETSA-based target engagement of taxanes as biomarkers for efficacy and resistance.

ABSTRACT: The use of taxanes has for decades been crucial for treatment of several cancers. A major limitation of these therapies is inherent or acquired drug resistance. A key to improved outcome of taxane-based therapies is to develop tools to predict and monitor drug efficacy and resistance in the clinical setting allowing for treatment and dose stratification for individual patients. To assess treatment efficacy up to the level of drug target engagement, we have established several formats of tubulin-specific Cellular Thermal Shift Assays (CETSAs). This technique was evaluated in breast and prostate cancer models and in a cohort of breast cancer patients. Here we show that taxanes induce significant CETSA shifts in cell lines as well as in animal models including patient-derived xenograft (PDX)

SUBMITTER: Langeback A 

PROVIDER: S-EPMC6920357 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature