Molecular mechanism and treatment progress of primary resistance to epidermal growth factor receptor-tyrosine kinase inhibitors in non-small cell lung cancer
10.12025/j.issn.1008-6358.2025.20250513
- VernacularTitle:非小细胞肺癌表皮生长因子受体酪氨酸激酶抑制剂原发性耐药分子机制及治疗进展
- Author:
Lu YAO
1
;
Yu HAN
1
;
Hanshuo MU
1
;
Yu ZHANG
1
Author Information
1. Department of Respiratory Medicine, The Brain Hospital Affiliated to Nanjing Medical University, Nanjing Chest Hospital, Nanjing 210029, Jiangsu, China.
- Publication Type:Review
- Keywords:
non-small cell lung cancer;
epidermal growth factor receptor;
tyrosine kinase inhibitor;
primary resistance
- From:
Chinese Journal of Clinical Medicine
2026;33(1):121-133
- CountryChina
- Language:Chinese
-
Abstract:
Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) block downstream signaling pathways by inhibiting receptor tyrosine kinase activity, consequently suppressing proliferation, invasion and metastasis of tumor cells. EGFR-TKIs have been proven to be highly effective in patients with late non-small cell lung cancer (NSCLC) harboring EGFR sensitive mutations, significantly better than chemotherapy. Third-generation EGFR-TKIs, such as osimertinib, have emerged as the first-line treatment for advanced NSCLC patients with sensitive EGFR mutations. However, there are still some patients who exhibit primary resistance upon initial treatment with EGFR-TKIs. The exact mechanism of primary resistance remains unknown, and may be related to factors such as the structure of EGFR mutation subtypes, concurrent mutations, BIM deletion polymorphism, and high expression of programmed cell death-ligand 1. This review summarizes the molecular mechanisms of primary resistance to EGFR-TKIs and discusses potential therapeutic strategies, with the goal of optimizing precision targeted therapy for NSCLC patients.
