表皮生长因子受体基因20号外显子插入突变型非小细胞肺癌的治疗现状与展望

The research status and development trend of EGFR gene exon 20 insertion mutant non-small cell lung cancer

自表皮生长因子受体(EGFR)基因突变被发现以来,酪氨酸激酶抑制剂(TKI)的应用拉开了EGFR阳性非小细胞肺癌精准靶向治疗的序幕。携带EGFR基因常见的两类经典代表性突变,即第19号外显子框内缺失突变和第21号外显子L858R点突变(约占所有EGFR突变的90%)的非小细胞肺癌患者,接受TKI靶向治疗的临床获益远远优于传统化疗。EGFR基因第20号外显子插入突变却与众不同,在剩余10%EGFR少见基因突变中为最常见的类型,且这类突变中的绝大多数对目前临床应用的第一、二、三代TKI原发耐药,临床预后差。目前,国际上亦缺乏针对此突变的深入研究和临床治疗指南。文章介绍了EGFR基因20号外显子插入突变型非小细胞肺癌的发病机制、氨基酸序列亚型和治疗现状,探讨了此突变在目前肺癌治疗领域所面临的挑战与展望。

The successful application of tyrosine kinase inhibitor(TKI)has kicked off the targeted therapy of epidermal growth factor receptor(EGFR)mutant non-small cell lung cancer(NSCLC)since the discovery of EGFR gene mutations.Patients harboring the two most classic representative mutations of EGFR gene including exon 19 in-frame deletion or exon 21 L858R mutation could get significant clinical benefits from EGFR-TKIs compared to traditional chemotherapy.Among other approximately 10%of EGFR gene mutation type,exon 20 insertion occupies the first place.Available research had demonstrated that EGFR exon 20 insertion in NSCLC was highly malignant and most insertion variants showed de novo drug resistance towards current approved 1st to 3rd generation EGFR-TKIs,with much poorer clinical prognosis.Currently,there is a lack of comprehensive research and clinical guideline on the treatment of this specific mutation.In this article,we review the pathogenesis,amino acid sequence variants and current management of EGFR exon 20 insertion mutant NSCLC.Moreover,we come up with the emphasis on the treatment challenges and further development of this rigid mutation in NSCLC.