KRAS突变的非小细胞肺癌的研究进展

Research Progress of KRAS Mutation in Non-small Cell Lung Cancer

肺癌是全球癌症相关死亡的主要原因。非小细胞肺癌(non-small cell lung cancer,NSCLC)占所有肺癌患者中的80%-85%,大多数肺癌患者在确诊时已处于晚期阶段。目前,基于驱动基因的靶向治疗的发展改变了晚期NSCLC患者的治疗模式。在NSCLC中,表皮生长因子受体突变(epidermal growth factor receptor,EGFR)和棘皮动物微管相关蛋白和间变性淋巴瘤激酶(echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase,EML4-ALK)融合已被验证为强大的生物标志物。众所周知KRAS也是NSCLC中最常见的突变致癌基因之一,尽管20多年前在NSCLC中发现了KRAS突变,迄今为止用于治疗KRAS突变的NSCLC患者的药物有很多,但目前还没有针对直接消除KRAS活性的选择性和特异性抑制剂。此外具有KRAS突变的NSCLC患者对大多数系统性治疗的反应性差。然而使用靶向药物针对活化的信号通路个体化治疗对KRAS突变的NSCLC患者的预后有很好疗效。此外KRAS突变在NSCLC中的预后和预测作用尚不清楚。在这篇综述中,我们重点讨论了KRAS突变的NSCLC的研究进展,包括分子生物学、临床病理特征、KRAS突变的预后和预测等方面,进而有助于提高临床工作者对KRAS突变的NSCLC的认知。。

Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small cell lung cancer（NSCLC） accounts for 80%-85% of all patients with lung cancer, the majority of patients with lung cancer at the time of diagnosis is in the advanced stage. The development of target therapy based on has changed the mode of treatment in patients with advanced NSCLC. In NSCLC, epidermal growth factor receptor mutation（EGFR） fusion with echinoderm microtubule-associated protein-like4-anaplastic lymphoma kinase（EML4-ALK） has been shown to be a powerful biomarker. It is well known that KRAS is also NSCLC one of the most common mutations in oncogenes, although more than 20 years ago KRAS mutation was found in NSCLC. At present, although there are many drugs used to treat NSCLC patients with KRAS mutation, there is no selective or specific inhibitor for the direct elimination of KRAS activity. NSCLC patients with KRAS mutation have poor responsiveness to most systemic therapy. However, individualized therapy for activated signaling pathways with targeted drugs has a good effect on the prognosis of NSCLC patients with KRAS mutation. In addition, the prognostic and predictive role of KRAS mutation in NSCLC remains unclear. In this review, we focus on the research progress of NSCLC with KRAS mutation, including molecular biology, clinicopathological features, prognosis and prediction of KRAS mutation, which will help to improve the understanding of NSCLC in KRAS mutation.