Mechanism of action biomarkers predicting response to AKT inhibition in the I-SPY 2 breast cancer trial.

ABSTRACT: The AKT inhibitor MK2206 (M) was evaluated in I-SPY 2 and graduated in the HER2+, HR-, and HR- HER2+ signatures. We hypothesized that AKT signaling axis proteins/genes may specifically predict response to M and tested 26 phospho-proteins and 10 genes involved in AKT-mTOR-HER signaling; in addition, we tested 9 genes from a previous study in the metastatic setting. One hundred and fifty patients had gene expression data from pretreatment biopsies available for analysis (M: 94, control: 56) and 138 had protein data (M: 87, control: 51). Logistic modeling was used to assess biomarker performance in pre-specified analysis. In general, phospho-protein biomarkers of activity in the AKT-mTOR-HER pathway appeared more predictive of response to M than gene expression or total protein biomarkers in

SUBMITTER: Wolf DM 

PROVIDER: S-EPMC7532145 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature