Inhibition of AKT enhances chemotherapy efficacy and synergistically interacts with targeting of the Inhibitor of apoptosis proteins in oesophageal adenocarcinoma.

ABSTRACT: The incidence of oesophageal adenocarcinoma (OAC) has risen six-fold in western countries over the last forty years but survival rates have only marginally improved. Hyperactivation of the PI3K-AKT-mTOR pathway is a common occurrence in OAC, driving cell survival, proliferation and resistance to chemotherapeutic agents. Inhibition of AKT has been explored as a treatment strategy with limited success and current inhibitors have failed to progress through clinical trials. Our study, describes a novel allosteric AKT inhibitor, ALM301, and demonstrates an enhancement of the efficacy of conventional chemotherapy when combined with ALM301 in OAC. Reduced sensitivity to ALM301 is associated with high expression of the Inhibitor of Apoptosis (IAP) family of proteins, particularly XIAP. Combined AK

SUBMITTER: Stevenson L 

PROVIDER: S-EPMC11686190 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature