药学学报, 2021, 56(5): 1201-1210
引用本文:
李润, 郭弘洁, 陈羲, 丁玲. 非小细胞肺癌的EGFR外显子20插入突变:分类及临床治疗研究进展[J]. 药学学报, 2021, 56(5): 1201-1210.
LI Run, GUO Hong-jie, CHEN Xi, DING Ling. EGFR exon 20 insertion mutation in non-small cell lung cancer:classification and clinical treatment research[J]. Acta Pharmaceutica Sinica, 2021, 56(5): 1201-1210.

非小细胞肺癌的EGFR外显子20插入突变:分类及临床治疗研究进展
李润1, 郭弘洁2, 陈羲2*, 丁玲2*
1. 浙江中医药大学, 浙江 杭州 310053;
2. 浙江大学药学院, 药理毒理研究所, 浙江 杭州 310058
摘要:
近年来,靶向治疗已成为晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)的标准治疗方案,但这种治疗方法对于那些具有表皮生长因子受体(epidermal growth factor receptor,EGFR)外显子20插入(ex20ins)突变的肿瘤患者效果非常有限。该插入突变是EGFR第三大常见突变,它缩小了药物结合口袋,赋予肿瘤对常用的EGFR酪氨酸激酶抑制剂(tyrosine kinase inhibitors,TKI)的内在抗性,致使第一代和第二代EGFR TKI的功效有限。迄今为止,尚未有获得批准的针对NSCLC EGFR外显子20插入突变的靶向治疗的药物。在这种情况下,研究新一代的EGFR TKI或采用双特异性抗体作为新的治疗策略,可能会为这些患者建立新的治疗标准。本文将总结迄今为止报道的所有有关外显子20插入对EGFR结构和其对EGFR抑制剂敏感性的影响,以及外显子20插入的NSCLC患者的治疗策略,希望为临床治疗提供参考。
关键词:    表皮生长因子受体      外显子20      插入突变      酪氨酸激酶抑制剂      临床治疗     
EGFR exon 20 insertion mutation in non-small cell lung cancer:classification and clinical treatment research
LI Run1, GUO Hong-jie2, CHEN Xi2*, DING Ling2*
1. Zhejiang Chinese Medical University, Hangzhou 310053, China;
2. Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
Abstract:
In recent years, targeted therapy has become the standard treatment for advanced non-small cell lung cancer (NSCLC), but this treatment method has very limited effect on patients with epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutation. This insertion mutation is the third most common mutation in EGFR. It shrinks the drug binding pocket and gives tumors inherent resistance to available EGFR tyrosine kinase inhibitors (TKIs), resulting in the limited efficiency of the first and second generation of EGFR tyrosine. So far, no targeted therapy has been approved for NSCLC patients with EGFR exon 20 insertion mutations, and there are still no drugs that have met clinical needs. In this case, new treatment strategies using new EGFR TKIs or bispecific antibodies may establish new treatment standards for these patients in the future. In this review, we will summarize all relevant exon 20 insertions reported so far on the structure of EGFR and its influence on EGFR inhibitor sensitivity, as well as the treatment strategies of exon 20 insertions in NSCLC patients, hoping to be a clinical treatment for reference.
Key words:    epidermal growth factor receptor    exon 20    insertion mutation    tyrosine kinase inhibitor    clinical treatment   
收稿日期: 2020-12-08
DOI: 10.16438/j.0513-4870.2020-1852
基金项目: 国家自然科学基金资助项目(81773754).
通讯作者: 丁玲,Tel:86-571-88208400,E-mail:ld362@zju.edu.cn;陈羲,E-mail:chenxii@zju.edu.cn
Email: ld362@zju.edu.cn;chenxii@zju.edu.cn
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