EGFR blockade confers sensitivity to pan-RAS inhibitors in KRAS-mutated cancers.

ABSTRACT:

Introduction

KRAS is one of the most commonly occurring mutated oncogene in human cancers. Development of KRAS G12C or G12D inhibitors exhibit promising clinical activities, but patients harboring other hotspot KRAS mutations cannot benefit from those strategies. Recent development in pan-RAS inhibitors have broad therapeutic implications and merit clinical investigation. However, intrinsic and acquired drug resistance caused by tumor heterogeneity greatly limit the clinical application, posing a significant challenge in this field.

Results

In this study, through CRISPR/Cas9 sgRNA screening using a human kinome sgRNA library, EGFR was discovered to correlate with the sensitivity of KRAS-mutated tumors to pan-RAS inhibitor RMC-7977. Through multiple in vitro cell proliferatio

SUBMITTER: Han J 

PROVIDER: S-EPMC12528223 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature