Kirsten大鼠肉瘤病毒癌基因突变非小细胞肺癌的治疗进展

Progress in the treatment of non-small cell lung cancer with Kirsten rat sarcoma virusoncogene mutations

Kirsten大鼠肉瘤病毒癌基因(KRAS)是人类恶性肿瘤中普遍出现的癌基因,但长期以来被定义为不可成药的靶点。KRAS突变型的非小细胞肺癌(NSCLC)是一种高度异质性疾病,KRAS主要功能为调节鸟嘌呤三核苷酸磷酸(GTP)和鸟嘌呤二核苷酸磷酸(GDP)之间的转换,在细胞增殖、迁移、肿瘤的发生发展中也发挥重要作用。近年来,随着KRAS G12C抑制剂(如sotorasib和adagrasib)的研发取得显著进展,极大地推动了针对KRAS G12C突变晚期NSCLC的治疗。文章将系统介绍KRAS突变NSCLC患者的临床特征、 KRAS的结构域与功能,以及相关治疗进展,重点就KRAS靶向及联合治疗研究进展进行总结和展望。

Kirsten rat sarcoma virus oncogene(KRAS)is a common oncogene found in human malignancies,but it has long been defined as an undruggable target.KRAS-mutant non-small cell lung cancer(NSCLC)is a highly heterogeneous disease,where KRAS primarily functions to regulate the conversion between guanosine triphosphate(GTP)and guanosine diphosphate(GDP),playing a significant role in cell proliferation,migration,and tumorigenesis.In recent years,significant progress has been made in the development of KRAS G12C inhibitors(such as sotorasib and adagrasib),greatly advancing the treatment of advanced NSCLC with KRAS G12C mutations.This article systematically reviews the clinical characteristics of patients with KRAS-mutant NSCLC,the structure and function of KRAS,and the related therapeutic advancements,with a focus on summarizing and projecting the research progress in KRAS-targeted and combination therapies.