Genetic Alterations in the PI3K/AKT Pathway and Baseline AKT Activity Define AKT Inhibitor Sensitivity in Breast Cancer Patient-derived Xenografts.

ABSTRACT:

Purpose

AZD5363/capivasertib is a pan-AKT catalytic inhibitor with promising activity in combination with paclitaxel in triple-negative metastatic breast cancer harboring PI3K/AKT-pathway alterations and in estrogen receptor-positive breast cancer in combination with fulvestrant. Here, we aimed to identify response biomarkers and uncover mechanisms of resistance to AZD5363 and its combination with paclitaxel.

Experimental design

Genetic and proteomic markers were analyzed in 28 HER2-negative patient-derived xenografts (PDXs) and in patient samples, and correlated to AZD5363 sensitivity as single agent and in combination with paclitaxel.

Results

Four PDX were derived from patients receiving AZD5363 in the clinic which exhibited concordant treatment response. Mutations

SUBMITTER: Gris-Oliver A 

PROVIDER: S-EPMC7814659 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature