肿瘤药学2025，Vol.15Issue(1)：90-98,9.DOI:10.3969/j.issn.2095-1264.2025.01.12
ALK阳性非小细胞肺癌靶向治疗耐药机制及治疗进展
Mechanisms of resistance to targeted therapy and therapeutic advances in ALK-positive non-small cell lung cancer
摘要
Abstract
Anaplastic lymphoma kinase(ALK)gene fusion mutation is a unique subtype of non-small cell lung cancer(NSCLC),accounting for 3%-7%of all NSCLC cases.Although ALK tyrosine kinase inhibitors(TKIs)such as crizotinib,alectinib,and lorlatinib have significantly improved the prognosis of patients,acquired resistance remains a major clinical challenge.Primary resistance to ALK-TKIs involves rare ALK fusion variants,ALK point mutations,coexisting driver gene mutations,and abnormal tumor microenvironments.Secondary resistance can be divided into ALK-dependent and ALK-in-dependent resistance.The former is mainly produced by kinase domain mutation,ALK amplification and other mecha-nisms,while the latter involves bypass signal activation and histological phenotype transformation(such as transformation to small cell lung cancer).To address the challenge of drug resistance,new-generation ALK-TKIs(such as fourth-genera-tion TPX-0131 and NVL-655)and combination therapies(such as immunotherapy,anti-angiogenic therapy,and chemo-therapy)have emerged as promising therapeutic options.Future advancements in ALK-positive NSCLC management will rely on optimizing drug selection and sequencing strategies,integrating resistance mutation profiling,and developing per-sonalized combination regimens to achieve precision oncology goals.关键词
非小细胞肺癌/间变性淋巴瘤激酶/靶向治疗/耐药/疗效Key words
Non-small cell lung cancer/Anaplastic lymphoma kinase/Targeted therapy/Drug resistance/Efficacy分类
医药卫生引用本文复制引用
董付瑶,彭文颖..ALK阳性非小细胞肺癌靶向治疗耐药机制及治疗进展[J].肿瘤药学,2025,15(1):90-98,9.基金项目
云南省科技厅2023年度昆医联合专项面上项目(202301AY070001-254). （202301AY070001-254）
