RAS/RAF突变与MSI状态在结直肠癌治疗中的研究进展

Research progress of RAS,RAF mutation and MSI status in the treatment of colorectal cancer

近几年,结直肠癌中的分子研究取得了相当大的进展,对如何通过分子表达的不同来选择最佳治疗方案也有了更深的认识。RAS/RAF基因是染色体不稳定性(CIN)通路中最重要的组成部分之一。最近的研究显示RAS/RAF突变的患者有机会接受靶向MAP激酶信号传导通路中的EGFR-KRAS/BRAF-MEK抑制剂的联合治疗,从而为预后不良的RAS/RAF突变患者提供一种新的治疗方式。日前,微卫星不稳定性(MSI)已经被确认为结直肠癌患者接受PD-1治疗的分子标志物。但是MSI对患者是否应接受免疫治疗的预测仍存在些许偏差,相信更为完美的预测靶点肿瘤突变负荷(TMB)将在不久的将来应用于指导临床进行免疫治疗。RAS/RAF突变及MSI状态的研究进展,为改善结直肠癌患者的预后提供了美好前景。

In recent years,many scholars have made considerable progress in molecular research on colorectal cancer,and also gained a deep understanding of how to choose the best treatment plan through different states of molecular expression. In previous studies,RAS/RAF mutations have been considered biomarkers of poor prognosis. However,recent studies have shown that patients with RAS/RAF mutations have the opportunity to undergo interventions with inhibitors,turning them into better indicators of prognosis. The expanded RAS test is the latest predictor of whether a patient can respond to cetuximab and panitumumab combined chemotherapy. Combination therapy with dual inhibitors of EGFR/BRAF or BRAF/MEK in the MAP kinase signaling pathway can also clearly increase the survival of patients with BRAF mutations. More and more evidence shows that Her-2 can not only be applied to the treatment of breast cancer,but also can provide targeted therapy for trastuzumab in Her-2 expanded colorectal cancer patients.Immunotherapy is a novel treatment strategy for colorectal cancer,and many scholars are devoting themselves to develop markers of immune checkpoint inhibitors. Recently,MSI has been identified as a molecular marker for PD-1 treatment in patients with colorectal cancer. However,there are still some deviations from MSI＇ s predictions,and it is believed that the more perfect marker TMB will be used to guide clinical immunotherapy soon. Our continuous understanding of biomarkers is constantly innovating and improving our treatment strategies for colorectal cancer. Although most patients with colorectal cancer still use conventional non-selective cytotoxic chemotherapeutic agents for treatment,more and more small subsets of patients with a certain genetic alteration will choose targeted therapies. It is believed that selective targeted drug therapy and immunotherapy will eventually replace traditional non-selective cytotoxic chemotherapy. In short,the simultaneous development of molecular markers and their latest therapeutic strategies provide great prospects for improving the prognosis of patients with colorectal cancer.