克里斯汀鼠肉瘤病毒基因（KRAS）突变是胰腺癌、结直肠癌和非小细胞肺癌等多种实体肿瘤的主要驱动因素。由于KRAS的复杂结构和缺乏明确的药物结合口袋，传统的KRAS靶向治疗一直被认为“难以成药”，这给研究和临床应用带来了巨大挑战。近期，针对KRAS G12C和G12D突变的多种小分子抑制剂已成功进入临床试验，并表现出良好的疗效和耐受性。就KRAS的调控和信号传导，主要总结靶向KRAS G12抑制剂的临床试验进展，以期为抑制剂的发展提供有益参考。尽管靶向KRAS的研究面临诸多挑战，但其在恶性肿瘤治疗中的巨大潜力使人充满期待，有望为患者提供新的治疗选择。未来的研究将进一步深入探讨KRAS突变的分子机制及其与肿瘤间的相互作用，以期开发更精准有效的治疗药物。

Kirsten rat sarcoma viral oncogene (KRAS) mutations are a major driver of a variety of solid tumors, including pancreatic cancer, colorectal cancer, and non-small cell lung cancer. Due to the complex structure of KRAS and the lack of a clear drug-binding pocket, traditional KRAS-targeted therapy has always been considered “difficult to make drugs”, which brings great challenges to research and clinical applications. Recently, small molecule inhibitors targeting KRAS G12C and G12D mutations have successfully entered clinical trials and have shown good efficacy and tolerability. This article summarizes the development and clinical trial progress of targeted KRAS G12 inhibitors on the regulation and signal transduction of KRAS, in order to provide useful reference for the development of inhibitors. Although the research of targeting KRAS faces many challenges, its huge potential in the treatment of malignant tumors is full of expectations, and it is expected to provide patients with new treatment options in the future. Future research will further explore the molecular mechanism of KRAS mutation and its interaction with tumors, with a view to developing more accurate and effective therapeutic drugs.

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