Advances in targeting KRAS mutations: A promising approach for the treatment of non‑small cell lung cancer (Review)

Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations are among the most frequent oncogenic drivers in cancer, particularly in non-small cell lung cancer (NSCLC).KRAS was previously considered an 'undruggable' target due to the protein's smooth molecular surface and the absence of obvious drug binding sites.However, the development of selective KRAS G12C inhibitors, such as sotorasib and adagrasib, together with progress in immunotherapy, have demonstrated potential clinical activity.Further understanding of the complex signaling networks driven by KRAS has revealed new opportunities to target this pathway directly or through rational combination strategies.The present review explored KRAS-targeted therapies and immunotherapies, including limitations, resistance mechanisms and the efficacy of combination regimens.Although there has been notable progress, concerns regarding optimal therapy combinations, resistance management and early treatment strategies remain.The present review demonstrated the need for continued research to address these challenges and improve outcomes for patients with KRAS-mutated NSCLC.Contents 1. Introduction 2. KRAS signaling pathways 3. Clinical significance of KRAS mutations in NSCLC 4. Targeting KRAS mutations in NSCLC 5. Advances in treating KRAS mutations in NSCLC 6. Clinical impact of KRAS co-mutations (STK11, TP53 and KEAP1) 7. Mechanisms of resistance to anti-KRAS therapies 8. Future directions 9. Conclusion