非小细胞肺癌中BRAF突变和共突变的方式及临床意义的研究进展

Research progress on the mode and clinical significance of BRAF mutation and co-mutation in non-small cell lung cancer

鼠类肉瘤病毒癌基因同源物B1(v-raf murine sarcoma viral oncogene homolog B1,BRAF)基因是非小细胞肺癌(NSCLC)重要的驱动基因之一。掌握BRAF蛋白结构、功能及其突变机制,是针对BRAF突变的NSCLC靶向治疗的基础。BRAF突变肺癌的靶向治疗的耐药,是其治疗过程中最大的挑战。研究发现,BRAF不仅能通过单基因突变诱导肺癌的发生,还能与其它NSCLC常见驱动基因发生共突变(如EGFR、KRAS和ALK等),并可能成为其靶向药物耐药的重要方式。因此,该文将综述BRAF突变及与其它基因共突变病例的分子和临床特点,为深入研究BRAF靶向治疗的耐药机制提供理论依据及可能的治疗策略。

Mouse sarcoma virus oncogene homologue B1(v-raf murine sarcoma viral oncogene homolog B1,BRAF)gene is one of the important driving genes of non-small cell lung cancer(NSCLC).Mastering the structure,function and mutation mechanism of BRAF protein is the basis of NSCLC targeted therapy for BRAF mutation.The drug resistance of targeted treatment of BRAF mutant lung cancer is the biggest challenge in the process of treatment.Studies have found that BRAF can not only induce lung cancer through single gene mutation,but also co-mutate with other common driving genes(such as EGFR,KRAS,ALK,etc.),and may become an important way for NSCLC to target drug resistance.Therefore,this article will review the molecular and clinical characteristics of BRAF mutation and its co-mutation with other genes,so as to provide theoretical basis and possible treatment strategies for further study of the mechanism of drug resistance in BRAF targeted therapy.