KRAS in Colorectal Cancer: Tumorigenesis, Surgical Implications and Evolving Treatment Target

Purpose: This review aims to provide an updated overview of Kirsten rat sarcoma viral oncogene homologue (KRAS) mutations in colorectal carcinoma (CRC), focusing on their role in tumorigenesis, prognostic implications, and recent advances in targeted therapy. Major findings: KRAS mutations occur in approximately 40% of colorectal cancers and play a central role in tumour initiation and progression through constitutive activation of MAPK pathways. Clinically, KRAS mutations are well established as predictors of resistance to anti-EGFR therapy. Increasing evidence also supports their role as prognostic biomarkers, with KRAS-mutant tumours associated with increased recurrence risk and reduced survival, including in patients undergoing hepatic metastasectomy. Therapeutically, recent advances, most notably KRAS G12C inhibitors and combination strategies targeting upstream or parallel pathways, have expanded treatment options, although efficacy varies across KRAS mutation subtypes. Conclusions: KRAS mutations have important implications for the behaviour, prognosis, and management of colorectal cancer. Integrating KRAS mutational status into clinical decision-making may enable more personalised prognostication and treatment strategies. Continued research is required to broaden effective targeted therapies for the diverse spectrum of KRAS-mutant disease.