Zhang Jinsong, Vokes Natalie, Li Man, Xu Jiachen, Bai Hua, Wang Jie, Wang Zhijie, Zhang Jianjun
State Key Laboratory of Molecular Oncology, CAMS Key Laboratory of Translational Research on Lung Cancer, 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, No. 17, Panjiayuannanli, Chaoyang District, Beijing 100021, China.
Department of Thoracic/Head and Neck Medical Oncology, Department of Genomic Medicine, The Lung Cancer Interception Program, The Lung Cancer Genomics Program, The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA.
Chin Med J Pulm Crit Care Med. 2024 Sep 16;2(3):151-161. doi: 10.1016/j.pccm.2024.08.002. eCollection 2024 Sep.
Targeted therapy has ushered in a new era of precision medicine for non-small cell lung cancer (NSCLC). Currently, epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) stand as the recommended first-line therapy for advanced NSCLC harboring sensitive mutations. Nevertheless, most patients inevitably confront the challenge of drug resistance. This phenomenon arises not solely from intrinsic alterations within cancer cells but also from the intricate dynamics of the tumor microenvironment and the complex interactions that occur between cancer cells and their immediate surroundings. This review consolidates the current knowledge regarding EGFR-TKI resistance mechanisms, with a specific emphasis on unraveling the role played by the tumor microenvironment. In addition, the review delineates strategic approaches to surmount TKI resistance, thereby enriching the understanding of the interplay between therapeutic agents and the intricate milieu surrounding cancer cells.
靶向治疗开创了非小细胞肺癌（NSCLC）精准医学的新时代。目前，表皮生长因子受体（EGFR）-酪氨酸激酶抑制剂（TKIs）是携带敏感突变的晚期NSCLC的推荐一线治疗药物。然而，大多数患者不可避免地面临耐药挑战。这种现象不仅源于癌细胞内部的内在改变，还源于肿瘤微环境的复杂动态以及癌细胞与其周围环境之间发生的复杂相互作用。本综述整合了关于EGFR-TKI耐药机制的现有知识，特别强调揭示肿瘤微环境所起的作用。此外，该综述还阐述了克服TKI耐药的策略方法，从而加深了对治疗药物与癌细胞周围复杂环境之间相互作用的理解。
