Synergistic Inhibition of Drug Resistant KRAS Mutant Non-Small Cell Lung Cancer by Co-Targeting AXL and SRC.

ABSTRACT:

Background/objectives

KRAS-mutated NSCLC has been targeted using monoclonal antibody (mAb) or tyrosine kinase inhibitor (TKI) therapies. However, in time, these mutations appear to develop resistance against the targeted antibodies and TKI treatments. One possible explanation is the activation of pro apoptotic pathways through the AXL-SRC-Akt axis. In this study, we identify AXL as the bypass resistant gene and investigate its role with KRAS and SRC activity.

Methods

In this study, we use Dasatinib and SGI-7079 to co-inhibit SRC and AXL respectively. In vitro studies were conducted using four cell lines, and AXL suppression was achieved using siRNA and in CRISPR-Cas9 mediated knockout models. Subsequently, we studied gene-protein expression analysis using Western blot, apopt

SUBMITTER: Mukherjee S 

PROVIDER: S-EPMC11816174 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature