克里斯汀鼠肉瘤病毒基因（KRAS）突變是胰腺癌、結(jié)直腸癌和非小細(xì)胞肺癌等多種實體腫瘤的主要驅(qū)動因素。由于KRAS的復(fù)雜結(jié)構(gòu)和缺乏明確的藥物結(jié)合口袋，傳統(tǒng)的KRAS靶向治療一直被認(rèn)為“難以成藥”，這給研究和臨床應(yīng)用帶來了巨大挑戰(zhàn)。近期，針對KRAS G12C和G12D突變的多種小分子抑制劑已成功進(jìn)入臨床試驗，并表現(xiàn)出良好的療效和耐受性。就KRAS的調(diào)控和信號傳導(dǎo)，主要總結(jié)靶向KRAS G12抑制劑的臨床試驗進(jìn)展，以期為抑制劑的發(fā)展提供有益參考。盡管靶向KRAS的研究面臨諸多挑戰(zhàn)，但其在惡性腫瘤治療中的巨大潛力使人充滿期待，有望為患者提供新的治療選擇。未來的研究將進(jìn)一步深入探討KRAS突變的分子機(jī)制及其與腫瘤間的相互作用，以期開發(fā)更精準(zhǔn)有效的治療藥物。

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.

R979.1