EGFR外显子20插入突变:研究现状与治疗新策略

EGFR Exon 20 Insertion Mutation:Research Status and New Treatment Strategies

作为非小细胞肺癌(non-small cell lung cancer,NSCLC)中重要的致癌驱动基因,表皮生长因子受体外显子20插入突变(epidermal growth factor receptor exon 20 insertion,EGFR ex20ins)具有独特蛋白构象,并且对传统EGFR酪氨酸激酶抑制剂(EGFR-tyrosine kinase inhibitors,EGFR-TKIs)原发耐药。近年来,靶向EGFR ex20ins的药物探索从未停止。莫博赛替尼与埃万妥单抗率先被美国食品药品监督管理局(Food and Drug Administration,FDA)获批用于EGFR ex20ins突变NSCLC患者,随后舒沃替尼等药物取得突破,联合治疗方案的探索也有所收获。多管齐下有望克服EGFR ex20ins耐药。因此,深入了解EGFR ex20ins的分子机制并评估新型药物的有效性与差异性至关重要。本文将对相关最新研究成果进行全面总结,以期为EGFR ex20ins突变患者精准治疗提供有价值的参考。

In non-small cell lung cancer(NSCLC),as an improtant oncogenic driver gene,epidermal growth factor receptor exon 20 insertion(EGFR ex20ins)has a unique protein structure and is primarily drug-resistant to traditional EGFR-tyrosine kinase inhibitors(EGFR-TKIs).In recent years,exploration of targeted therapy for EGFR ex20ins has never stopped.Firstly Mobocertinib and Amivantamab obtained approval from U.S.Food and Drug Administration(FDA)for EGFR ex20ins mutant NSCLC patients,then other drugs,such as Sunvozertinib,made breakthroughs and combination therapies also obtained gains.Multi-pronged measures are hopeful to overcome EGFR ex20ins drug resistance.As mentioned above,it’s definitely important to gain deeper understanding of molecular mechanism of EGFR ex20ins and assess effect and difference between novel drugs.This review is devoted to make a summary about newest achievement so to provide valuable reference about precise therapy for patients with EGFR ex20ins.