中国肺癌杂志2025，Vol.28Issue(7)：521-532,12.DOI:10.3779/j.issn.1009-3419.2025.106.21
氧化还原平衡稳态调控第三代非小细胞肺癌EGFR-TKIs耐药的研究进展
Research Progress on the Regulation of Third-generation EGFR-TKIs Resistance in Non-small Cell Lung Cancer by Redox Homeostasis
摘要
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 oxy-gen 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 shiftin NSCLC therapy from single-target inhibition toward multi-dimensional metabolic remodeling in the context of precision medicine.关键词
肺肿瘤/耐药性/表皮生长因子受体-酪氨酸激酶抑制剂/奥希替尼/活性氧/氧化还原稳态Key words
Lung neoplasms/Drug resistance/Epidermal growth factor receptor-tyrosine kinase inhibitors/Osimertinib/Reactive oxygen species/Redox homeostasis引用本文复制引用
罗婷,方晨,邱峰..氧化还原平衡稳态调控第三代非小细胞肺癌EGFR-TKIs耐药的研究进展[J].中国肺癌杂志,2025,28(7):521-532,12.基金项目
This study was supported by the grant from the National Natural Science Foundation of China(No.82460598) 本文受国家自然科学基金项目(No.82460598)资助 （No.82460598）
