Research Progress on the Regulation of Third-generation EGFR-TKIs Resistance
in Non-small Cell Lung Cancer by Redox Homeostasis.
10.3779/j.issn.1009-3419.2025.106.21
- Author:
Ting LUO
1
;
Chen FANG
1
;
Feng QIU
1
Author Information
1. Department of Medical Oncology, The First Affiliated Hospital of Nanchang University, Nanchang 330000, China.
- Publication Type:English Abstract
- Keywords:
Drug resistance;
Epidermal growth factor receptor-tyrosine kinase inhibitors;
Lung neoplasms;
Osimertinib;
Reactive oxygen species;
Redox homeostasis
- MeSH:
Humans;
Carcinoma, Non-Small-Cell Lung/genetics*;
ErbB Receptors/genetics*;
Drug Resistance, Neoplasm/drug effects*;
Lung Neoplasms/genetics*;
Oxidation-Reduction/drug effects*;
Homeostasis/drug effects*;
Protein Kinase Inhibitors/therapeutic use*;
Reactive Oxygen Species/metabolism*;
Animals
- From:
Chinese Journal of Lung Cancer
2025;28(7):521-532
- CountryChina
- Language:Chinese
-
Abstract:
Non-small cell lung cancer (NSCLC) ranks among the most lethal malignancies worldwide. The clinical application of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have successfully revolutionized the treatment paradigm for EGFR-mutant NSCLC, significantly prolonging progression-free survival and establishing EGFR-TKIs as the standard first-line therapy for advanced lung adenocarcinoma. However, acquired resistance remains a major obstacle to sustained clinical benefit, with mechanisms that are highly heterogeneous. A phenomenon of "oxidative stress compensation" is commonly observed in EGFR-TKIs-resistant cells, where in redox homeostasis, through the precise regulation of reactive oxygen species (ROS) generation and elimination, plays a pivotal role in maintaining the balance between tumor cell proliferation and apoptosis. This review aims to innovatively construct a theoretical framework describing how dynamic redox regulation influences resistance to third-generation EGFR-TKIs. It focuses on the multifaceted roles of ROS in both EGFR-dependent and EGFR-independent resistance mechanisms, and further explores therapeutic strategies that target ROS kinetic thresholds and antioxidant systems. These insights not only propose an innovative "metabolic checkpoint" regulatory pathway to overcome acquired resistance to third-generation EGFR-TKIs, but also lay a molecular foundation for developing the redox biomarker-based dynamic therapeutic decision-making systems, thereby facilitating a shift in NSCLC therapy from single-target inhibition toward multi-dimensional metabolic remodeling in the context of precision medicine.
.
