Fu Shenao, Ma Jiayao, Cai Changjing, Tan Jun, Deng Xiangying, Shen Hong, Zeng Shan, Chen Yihong, Han Ying
Department of Oncology, Xiangya Hospital, Central South University, Changsha, China.
Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China.
J Exp Clin Cancer Res. 2025 Jul 3;44(1):189. doi: 10.1186/s13046-025-03444-1.
In recent years, the development of targeted therapies for tumors with KRAS mutations has progressed rapidly, rendering the notion of KRAS as "undruggable" outdated. However, targeted therapies for KRAS mutations still face numerous challenges, including resistance, efficacy concerns, toxicity issues, and hurdles in drug development. Exploring alternative treatment modalities is thus essential. Extensive research has demonstrated that KRAS mutations significantly influence the immune microenvironment, presenting both challenges and opportunities for immunotherapy. Interestingly, it has been observed that different KRAS mutations and co-mutation subtypes exhibit significant variations in their immunological microenvironments, which undoubtedly impact immunotherapy choices. Here, we review the history of KRAS-targeted therapy, highlighting existing challenges, and summarize changes in the immune microenvironment of KRAS-mutated cancers and their potential therapeutic targets. We compare differences in the immune microenvironment across various mutation types and co-mutation subtypes, and offer perspectives on future research directions.
近年来,针对KRAS突变肿瘤的靶向治疗发展迅速,使得KRAS“不可成药”的观念过时。然而,KRAS突变的靶向治疗仍面临诸多挑战,包括耐药性、疗效问题、毒性问题以及药物研发中的障碍。因此,探索替代治疗方式至关重要。大量研究表明,KRAS突变显著影响免疫微环境,这为免疫治疗带来了挑战和机遇。有趣的是,人们观察到不同的KRAS突变和共突变亚型在其免疫微环境中表现出显著差异,这无疑会影响免疫治疗的选择。在此,我们回顾KRAS靶向治疗的历史,突出当前存在的挑战,并总结KRAS突变癌症免疫微环境的变化及其潜在治疗靶点。我们比较不同突变类型和共突变亚型的免疫微环境差异,并对未来研究方向提出展望。