鼠肉瘤病毒癌基因突变非小细胞肺癌靶向治疗 研究进展

Research progress on targeted therapy of Kirsten rat sarcoma virus oncogene mutation in non-small cell lung cancer

鼠肉瘤病毒癌基因(KRAS)突变是非小细胞肺癌中最常见的驱动基因突变之一,尽管在几十年前就已经发现KRAS基因突变,但由于其独特的生物特性,靶向治疗KRAS基因突变非小细胞肺癌一直面临瓶颈。然而新型KRAS G12C抑制剂的面世打破了这一僵局,使KRAS基因突变非小细胞肺癌靶向治疗得到进一步发展。目前国内外靶向KRAS突变非小细胞肺癌的研究机制主要是抑制膜定位、直接抑制KRAS基因、靶向抑制KRAS下游信号及抑制KRAS突变协同致死基因等。本综述概述KRAS基因突变非小细胞肺癌靶向治疗的研究进展,以便于临床医师更加深入了解这一特殊类型非小细胞肺癌的靶向治疗。

Kirsten rat sarcoma viral oncogene(KRAS)mutation is one of the most common driver gene mutations in non-small cell lung cancer.Although KRAS mutation was discovered decades ago,target therapy of non-small cells with KRAS mutations has been a bottleneck due to their unique biological characteristics.However,the emergence of new KRAS G12C inhibitors broke this deadlock and further developed targeted therapy for non-small cell lung cancer with mutations in the KRAS gene.The research mechanism of targeting KRAS mutant non-small cell lung cancer at home and abroad is mainly to inhibit membrane localization,directly inhibit KRAS gene,target inhibition of KRAS downstream signals,and inhibit KRAS mutation co-lethal genes.This review summarizes the research progress of targeted therapy for non-small cell lung cancer with mutations in the KRAS gene,so that clinicians can have a deeper understanding of targeted therapy for this particular type of non-small cell lung cancer.