Overcoming EGFR-TKI resistance by targeting the tumor microenvironment

Jinsong Zhang; Natalie Vokes; Man Li; Jiachen Xu; Hua Bai; Jie Wang; Zhijie Wang; Jianjun Zhang

doi:10.1016/j.pccm.2024.08.002

Overcoming EGFR-TKI resistance by targeting the tumor microenvironment

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.

Authors

Jinsong Zhang¹, Natalie Vokes², Man Li¹, Jiachen Xu¹, Hua Bai¹, Jie Wang³, Zhijie Wang¹, Jianjun Zhang²

Affiliations

¹ 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.
² 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.
³ Shanxi Cancer Hospital (Shanxi Cancer Institute), Cancer Hospital of Chinese Academy of Medical Sciences Shanxi Hospital, Shanxi Medical University Affiliated Hospital, Taiyuan, Shanxi 030013, China.

Abstract

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 EGFR 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.

Keywords: Drug resistance; Epidermal growth factor receptor; Epidermal growth factor receptor-tyrosine kinase inhibitor; Non-small cell lung cancer; Tumor microenvironment.

Publication types

Review