Targeting KRAS in colorectal cancer (Review)

RAS genes play crucial roles in regulating important biological processes such as cell growth, differentiation, and apoptosis in normal cells. When RAS genes undergo mutations or abnormal expression, they can become oncogenic drivers, and the oncogenic mechanism of KRAS mutations which drive cancer progression is highly complex. Colorectal cancer carrying KRAS mutation genes often exhibits poor prognosis. Despite the advent of KRAS G12C inhibitors, monotherapy demonstrates suboptimal clinical efficacy in colorectal cancer, which is attributed to primary resistance and limited coverage of prevalent KRAS mutations (such as G12D and G12V). Notably, combinatorial regimens integrating KRASG12C inhibitors with EGFR monoclonal antibodies (such as cetuximab) have doubled objective response rates, highlighting synergistic therapeutic potential.