Lung cancer remains the leading cause of cancer incidence and mortality globally. Non-small cell lung cancer (NSCLC) constitutes approximately 85% of all lung cancer cases; designing treatment strategies for this disease is a significant focus. The KRAS gene is notably associated with a high mutation frequency in NSCLC, with the KRAS G12C subtype being the most prevalent. In recent years, several KRAS G12C inhibitors have received market approval and have shown promising antitumor efficacy; however, both primary and acquired resistance have hindered their long-term effectiveness. Therefore, a thorough investigation of the mechanisms underlying these resistance patterns, alongside the exploration of effective combination therapy strategies, is essential for enhancing patient prognosis. This article provides a systematic review of the resistance mechanisms to targeted therapies and the combination therapy strategies for KRAS G12C-mutated NSCLC, serving as a valuable reference for future research.

Yuxuan Feng, Shu Zhang, Xiaochuan Li, Xiaoqun Duan, Wei Yang. Mechanisms of Resistance to Targeted Therapy and Advances in Combination Therapy for KRAS G12C Non-Small Cell Lung Cancer. International Journal of Frontiers in Medicine (2026), Vol. 8, Issue 1: 73-80. https://doi.org/10.25236/IJFM.2026.080109.

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