Molecular mechanisms of acquired resistance to EGFR tyrosine kinase inhibitors in non-small cell lung cancer

IF 21.7 1区医学 Q1 PHARMACOLOGY & PHARMACY

Drug Resistance Updates Pub Date : 2025-06-09 DOI:10.1016/j.drup.2025.101266

Zhenfang Du , Hongfei Kan , Jinghan Sun , Yue Liu , Jiahui Gu , Shugela Akemujiang , Yudi Zou , Lufan Jiang , Qinzhuo Wang , Chen Li , Lei Luo , Yunkai Zhang , Hong Fan , Pengfei Luo , Bo Wang

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Abstract

Tyrosine kinase inhibitors (TKIs) have revolutionized the management of epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). Despite the initially favorable outcomes, these patients inevitably acquire resistance to EGFR-TKIs. The molecular mechanism of the acquired resistance is highly complex and heterogeneous, and can be generalized as three categories, including EGFR pathway reactivation (re-engagement of EGFR downstream), EGFR pathway bypass (adoption of a parallel pathway to re-engage the downstream transcriptional oncogenic output of the original EGFR), and EGFR pathway indifference (acquirement of a cellular state alternate to the original EGFR-driven output). This review summarizes the recent progress on the identification and understanding of the acquired resistance mechanisms to EGFR-TKIs in patients with NSCLC. The potential strategies to delay or overcome the acquired resistance are also discussed.

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非小细胞肺癌对EGFR酪氨酸激酶抑制剂获得性耐药的分子机制

酪氨酸激酶抑制剂（TKIs）已经彻底改变了表皮生长因子受体（EGFR）突变的非小细胞肺癌（NSCLC）的治疗。尽管最初结果良好，但这些患者不可避免地对EGFR-TKIs产生耐药性。获得性耐药的分子机制是高度复杂和异质性的，可以概括为三类，包括EGFR途径再激活（EGFR下游重新参与），EGFR途径旁路（采用平行途径重新参与原始EGFR的下游转录致癌输出），以及EGFR途径无差异（获得替代原始EGFR驱动输出的细胞状态）。本文综述了近年来对NSCLC患者EGFR-TKIs获得性耐药机制的研究进展。本文还讨论了延迟或克服获得性耐药性的潜在策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Drug Resistance Updates 医学-药学

CiteScore

26.20

自引率

11.90%

发文量

审稿时长

29 days

期刊介绍： Drug Resistance Updates serves as a platform for publishing original research, commentary, and expert reviews on significant advancements in drug resistance related to infectious diseases and cancer. It encompasses diverse disciplines such as molecular biology, biochemistry, cell biology, pharmacology, microbiology, preclinical therapeutics, oncology, and clinical medicine. The journal addresses both basic research and clinical aspects of drug resistance, providing insights into novel drugs and strategies to overcome resistance. Original research articles are welcomed, and review articles are authored by leaders in the field by invitation. Articles are written by leaders in the field, in response to an invitation from the Editors, and are peer-reviewed prior to publication. Articles are clear, readable, and up-to-date, suitable for a multidisciplinary readership and include schematic diagrams and other illustrations conveying the major points of the article. The goal is to highlight recent areas of growth and put them in perspective. *Expert reviews in clinical and basic drug resistance research in oncology and infectious disease *Describes emerging technologies and therapies, particularly those that overcome drug resistance *Emphasises common themes in microbial and cancer research