AKT mutant allele-specific activation dictates pharmacologic sensitivities.

ABSTRACT: AKT- a key molecular regulator of PI-3K signaling pathway, is somatically mutated in diverse solid cancer types, and aberrant AKT activation promotes altered cancer cell growth, survival, and metabolism^1-8. The most common of AKT mutations (AKT1 E17K) sensitizes affected solid tumors to AKT inhibitor therapy^7,8. However, the pathway dependence and inhibitor sensitivity of the long tail of potentially activating mutations in AKT is poorly understood, limiting our ability to act clinically in prospectively characterized cancer patients. Here we show, through population-scale driver mutation discovery combined with functional, biological, and therapeutic studies that some but not all missense mutations activate downstream AKT effector pathways in a growth factor-independ

SUBMITTER: Shrestha Bhattarai T 

PROVIDER: S-EPMC9018718 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature