The Dual PI3K/mTOR Pathway Inhibitor GDC-0084 Achieves Antitumor Activity in PIK3CA-Mutant Breast Cancer Brain Metastases.

ABSTRACT:

Purpose

Previous studies have shown that the PI3K/Akt/mTOR pathway is activated in up to 70% of breast cancer brain metastases, but there are no approved agents for affected patients. GDC-0084 is a brain penetrant, dual PI3K/mTOR inhibitor that has shown promising activity in a preclinical model of glioblastoma. The aim of this study was to analyze the efficacy of PI3K/mTOR blockade in breast cancer brain metastases models.Experimental Design: The efficacy of GDC-0084 was evaluated in PIK3CA-mutant and PIK3CA wild-type breast cancer cell lines and the isogenic pairs of PIK3CA wild-type and mutant (H1047R/+) MCF10A cells in vitro. In vitro studies included cell viability and apoptosis assays, cell-cycle analysis, and Western blots. In viv

SUBMITTER: Ippen FM 

PROVIDER: S-EPMC6685218 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature