Identification of Candidate Alterations Mediating KRASG12C Inhibitor Resistance in Advanced Colorectal and Pancreatic Cancers.

ABSTRACT:

Purpose

KRAS G12C inhibitors can treat KRASG12C-mutant advanced colorectal cancers and pancreatic ductal adenocarcinomas (PDAC), but alterations in Kirsten rat sarcoma (KRAS), EGFR, BRAF, MAP2K1, and other genes bypass KRAS inhibition and reduce therapy efficacy. Our study evaluates the genetic landscape of candidate primary resistance alterations relevant to KRAS targeting in KRASG12C-mutant colorectal cancer and PDAC.

Experimental design

We analyzed two cohorts (national database and Mayo) of patients with advanced colorectal cancer or PDAC tested with next-generation sequencing of ctDNA via Guardant360. Cohorts were divided into three groups: KRASG12C alone (KRASG12C without a resistance gene), KRASG12C with resistance (KRASG12C and ≥1 candidate resistance gene), and KRAS

SUBMITTER: Jazieh K 

PROVIDER: S-EPMC11879249 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature