The PI3K-AKT-mTOR axis persists as a therapeutic dependency in KRAS^G12D-driven non-small cell lung cancer.

ABSTRACT:

Introduction

KRAS^G12C and KRAS^G12D inhibitors represent a major translational breakthrough for non-small cell lung cancer (NSCLC) and cancer in general by directly targeting its most mutated oncoprotein. However, resistance to these small molecules has highlighted the need for rational combination partners necessitating a critical understanding of signaling downstream of KRAS mutant isoforms.

Methods

We contrasted tumor development between Kras^G12C and Kras^G12D genetically engineered mouse models (GEMMs). To corroborate findings and determine mutant subtype-specific dependencies, isogenic models of Kras^G12C and Kras^G12D initiation and adaptation were profiled by RNA sequencing. We also employed cell line model

SUBMITTER: McDaid WJ 

PROVIDER: S-EPMC11555833 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature