Frisch Austin, Martin Eric, Kim So Yeon, Riess Jonathan W, Sen Triparna, Karim Nagla
Inova Fairfax Department of Internal Medicine, Inova Fairfax Hospital, Fairfax, VA 22042, United States.
Yale Cancer Center, Yale School of Medicine, New Haven, CT 06510, United States.
Oncologist. 2025 Jun 4;30(6). doi: 10.1093/oncolo/oyaf153.
Non-small cell lung cancer (NSCLC) is among one of the most common and deadliest malignancies worldwide. With this new era of precision medicine, oncogenic driver genes and immunotherapy have changed the way we classify and treat this disease. Among these genes, the Kirsten rat sarcoma virus (KRAS) gene is the most mutated in NSCLC and has been the focus of numerous clinical trials for targeted therapy over the past few years. Here, we present an in-depth literature review of past, present, and future KRAS mutated NSCLC treatment with KRAS inhibitor monotherapy and combinatorial approaches including immunotherapy. The molecular biology behind KRAS targeted therapy is discussed while highlighting the difficulties of KRAS inhibitor treatment, including resistance, and the next steps needed to overcome them.
非小细胞肺癌(NSCLC)是全球最常见、最致命的恶性肿瘤之一。在这个精准医学的新时代,致癌驱动基因和免疫疗法改变了我们对这种疾病的分类和治疗方式。在这些基因中, Kirsten 大鼠肉瘤病毒(KRAS)基因在NSCLC中突变最为频繁,并且在过去几年一直是众多靶向治疗临床试验的重点。在此,我们对过去、现在和未来KRAS突变型NSCLC采用KRAS抑制剂单药治疗以及包括免疫疗法在内的联合治疗方法进行了深入的文献综述。讨论了KRAS靶向治疗背后的分子生物学,同时强调了KRAS抑制剂治疗的困难,包括耐药性,以及克服这些困难所需的下一步措施。