Yang G J, Wang Y
Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Zhonghua Zhong Liu Za Zhi. 2020 Jan 23;42(1):22-29. doi: 10.3760/cma.j.issn.0253-3766.2020.01.003.
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 1(st) to 3(rd) 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.
自发现表皮生长因子受体（EGFR）基因突变以来，酪氨酸激酶抑制剂（TKI）的成功应用开启了EGFR突变非小细胞肺癌（NSCLC）的靶向治疗。与传统化疗相比，携带EGFR基因两种最典型代表性突变（包括外显子19框内缺失或外显子21 L858R突变）的患者可从EGFR-TKIs中获得显著的临床益处。在其他约10%的EGFR基因突变类型中，外显子20插入位居首位。现有研究表明，NSCLC中的EGFR外显子20插入具有高度恶性，大多数插入变体对目前批准的第一代至第三代EGFR-TKIs表现出原发性耐药，临床预后较差。目前，针对这种特定突变的治疗缺乏全面的研究和临床指南。在本文中，我们综述了EGFR外显子20插入突变NSCLC的发病机制、氨基酸序列变体及当前治疗情况。此外，我们还强调了NSCLC中这种难治性突变的治疗挑战和进一步发展。
