KEAP1 mutations as key crucial prognostic biomarkers for resistance to KRAS-G12C inhibitors.

ABSTRACT:

Background

KRAS-G12C inhibitors mark a notable advancement in targeted cancer therapies, yet identifying predictive biomarkers for treatment efficacy and resistance remains essential for optimizing clinical outcomes.

Methods

This systematic meta-analysis synthesized studies available through September 2024 across PubMed, Cochrane Library, SpringerLink, and Embase. Using CRISPR/Cas9 technology, this study generated cells with KEAP1 and STK11 knockouts, and utilized lentiviral vectors to overexpress PD-L1. Cellular sensitivity to KRAS-G12C inhibitors-AMG510, MRTX849, and JAB-21822-was evaluated through CCK-8 assays. Comprehensive bioinformatics analyses on stably transfected cell lines were conducted to elucidate pathways mediating resistance.

Results

Analysis of 13 stu

SUBMITTER: Tian L 

PROVIDER: S-EPMC11748609 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature