Biomarkers of response to Akt inhibitor MK-2206 in breast cancer.

ABSTRACT:

Purpose

We tested the hypothesis that allosteric Akt inhibitor MK-2206 inhibits tumor growth, and that PTEN/PIK3CA mutations confer MK-2206 sensitivity.

Experimental design

MK-2206 effects on cell signaling were assessed in vitro and in vivo. Its antitumor efficacy was assessed in vitro in a panel of cancer cell lines with differing PIK3CA and PTEN status. Its in vivo efficacy was tested as a single agent and in combination with paclitaxel.

Results

MK-2206 inhibited Akt signaling and cell-cycle progression, and increased apoptosis in a dose-dependent manner in breast cancer cell lines. Cell lines with PTEN or PIK3CA mutations were significantly more sensitive to MK-2206; however, several lines with PTEN/PIK3CA mutations were MK-2206 resistant. siRNA knockdown of PTEN

SUBMITTER: Sangai T 

PROVIDER: S-EPMC3772348 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature