非小细胞肺癌获得性耐药和表皮生长因子受体靶向治疗耐受机制研究进展

doi:10.19803/j.1672-8629.20240287

中国药物警戒 ›› 2024, Vol. 21 ›› Issue (10): 1081-1086.
DOI: 10.19803/j.1672-8629.20240287

非小细胞肺癌获得性耐药和表皮生长因子受体靶向治疗耐受机制研究进展

谢思华¹, 高志超^1,2, 张维¹, 邢佳会¹, 梁经纬^1,3#, 孟繁浩^1,*

¹中国医科大学药学院,小分子靶向抗肿瘤药物研究与开发重点实验室,辽宁沈阳 110122;
²辽宁省肿瘤医院肿瘤内科,辽宁沈阳 110044;
³海南医学院药学院,海南省热带药用植物研发重点实验室,海南海口 571199

收稿日期:2024-04-30 出版日期:2024-10-15 发布日期:2024-10-14
通讯作者: ^*孟繁浩,男,二级教授·博导,药物研究与开发。E-mail：fhmeng@cmu.edu.cn孟繁浩,药学博士,二级教授,博士研究生导师。国务院政府特殊津贴专家、辽宁省特聘教授。中国药理学会抗炎免疫药理学专业委员会常委、辽宁省药学会药物化学专业委员会副主任委员、辽宁省生物技术协会理事、辽宁省突发公共卫生事件专家咨询委员会专家。主编《药物化学》《药物设计学》等高等医药院校统编教材16部。已发表学术论文200余篇,发明专利35项,计算机软件著作权登记证书3项,新药证书10项。获得辽宁省科技进步一等奖/二等奖、辽宁省普通高等教育教学一等奖、辽宁省自然科学学术成果二等奖等多项成果。任《中国药物警戒》等期刊编委。^#为共同通信作者。
作者简介:谢思华,女,在读硕士,药物耐药机制研究。
基金资助:
国家自然科学基金资助项目（82103998）

Research progress in mechanisms of acquired drug resistance and EGFR-targeted therapy tolerance in non-small cell lung cancer

XIE Sihua¹, GAO Zhichao^1,2, ZHANG Wei¹, XING Jiahui¹, LIANG Jingwei^1,3#, MENG Fanhao^1,*

¹School of Pharmacy/Key Laboratory of Research and Development of Small Molecule Targeted Antitumor Drugs, China Medical University, Shenyang Liaoning 110122, China;
²Department of Medical Oncology, Cancer Hospital & Institute, Shenyang Liaoning 110044, China;
³School of Pharmacy, Hainan Medical University, Key Laboratory of Research and Development of Tropical Medicinal Plants, Hainan Province, Haikou Hainan 571199, China

Received:2024-04-30 Online:2024-10-15 Published:2024-10-14

摘要/Abstract

摘要： 目的探讨靶向表皮生长因子受体（EGFR）的特异性酪氨酸激酶抑制剂（EGFR-TKIs）在治疗该靶点突变的非小细胞肺癌（NSCLC）中的研究进展。方法重点讨论EGFR的靶向治疗方案,并详细阐述EGFR-TKIs的耐药机制,以及耐药持久性（DTP）细胞的特征和EGFR突变导致NSCLC耐药的机制基础。结果 EGFR靶向治疗疗效显著,但会引起药物耐受或耐药细胞的出现,最终导致肿瘤复发。结论深入研究药物耐受性和获得性耐药的根本原因,有助于提高癌症治疗的效果。

关键词: 非小细胞肺癌, 表皮生长因子受体, 靶向治疗, 酪氨酸激酶抑制剂, 药物耐受性, 获得性耐药

Abstract: Objective To summarize the progress in treatment of non-small cell lung cancer (NSCLC) with mutations by specific tyrosine kinase inhibitors (EGFR-Tkis) that target the epidermal growth factor receptor (EGFR). Methods Targeted therapies with EGFR currently available were highlighted. The common mechanisms of EGFR-TKIs resistance were elaborated. The characteristics of drug-tolerant persister (DTP) cells and the mechanism of EGFR mutation leading to drug resistance in NSCLC were discussed. Results EGFR-targeted therapies could cause drug-resistance or drug-resistant cells, ultimately leading to tumor recurrence. Conclusion Insights into drug tolerance and underlying causes of resistance can help improve the effectiveness of cancer treatment.

Key words: non-small cell lung cancer(NSCLC), epidermal growth factor receptor(EGFR), targeted therapy, tyrosine kinase inhibitors(EGFR-Tkis), drug tolerance, acquired drug resistance

中图分类号:

R979.1

谢思华, 高志超, 张维, 邢佳会, 梁经纬, 孟繁浩. 非小细胞肺癌获得性耐药和表皮生长因子受体靶向治疗耐受机制研究进展[J]. 中国药物警戒, 2024, 21(10): 1081-1086.

XIE Sihua, GAO Zhichao, ZHANG Wei, XING Jiahui, LIANG Jingwei, MENG Fanhao. Research progress in mechanisms of acquired drug resistance and EGFR-targeted therapy tolerance in non-small cell lung cancer[J]. Chinese Journal of Pharmacovigilance, 2024, 21(10): 1081-1086.

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非小细胞肺癌获得性耐药和表皮生长因子受体靶向治疗耐受机制研究进展

Research progress in mechanisms of acquired drug resistance and EGFR-targeted therapy tolerance in non-small cell lung cancer

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