非小细胞肺癌治疗后重复活检研究进展及意义OA
Research Progress and Clinical Significance of Repeated Biopsy after Treatment for Non-Small Cell Lung Cancer
非小细胞肺癌(non-small cell lung cancer,NSCLC)约占全部肺癌的80%~85%,多数患者确诊时已处于中晚期阶段.随着驱动基因的发现及靶向治疗的发展,NSCLC 治疗模式进入精准医学时代,但获得性耐药几乎不可避免,使治疗后疾病管理面临新的挑战.重复活检通过在疾病进展或耐药后重新获取肿瘤组织或体液样本,能够动态评估肿瘤分子特征与组织学变化,已成为指导个体化治疗的重要策略.研究表明,重复活检可揭示表皮生长因子受体酪氨酸激酶抑制剂耐药相关突变、间变性淋巴瘤激酶域次级突变及间质-上皮转化因子旁路激活等分子机制,同时识别小细胞肺癌或鳞癌转化等非基因性耐药模式,为后续靶向治疗序贯应用、化疗或免疫治疗调整提供关键依据.此外,液体活检技术快速发展,基于循环肿瘤 DNA、循环肿瘤细胞、DNA 甲基化、代谢组学及肿瘤教育血小板等新型标志物的检测,实现了对肿瘤演化的微创、动态监测,成为组织活检的重要补充.总体而言,重复活检从分子与表型双层面解析 NSCLC 耐药机制,有助于优化治疗决策并推动精准治疗策略的持续发展.未来,组织活检与液体活检的协同应用及检测技术的进步,有望进一步提升 NSCLC 个体化管理水平与临床获益.
Non-small cell lung cancer(NSCLC)accounts for approximately 80%~85%of all lung cancer cases,and most patients are diagnosed at an advanced stage.With the discovery of driver genes and the development of targeted thera-pies,the treatment paradigm of NSCLC has entered the era of precision medicine.However,acquired resistance to targeted therapies is almost inevitable,posing significant challenges for disease management after treatment.Rebiopsy,which in-volves obtaining tumor tissue or bodily fluid samples after disease progression or resistance,enables dynamic assessment of tumor molecular characteristics and histological changes and has become an important strategy for guiding individualized treat-ment.Studies have shown that repeated biopsy can identify epidermal growth factor receptor-tyrosine kinase inhibitor resist-ance-related mutations,secondary mutations in the anaplastic lymphoma kinase domain,and mesenchymalepithelial transition factor bypass activation,as well as detect non-genetic resistance patterns such as histological transformation to small cell lung cancer or squamous cell carcinoma.These findings provide critical evidence for the sequential application of subsequent tar-geted therapy and the adjustment of chemotherapy or immunotherapy.In addition,rapid advances in liquid biopsy technolo-gies have enabled minimally invasive and dynamic monitoring of tumor evolution through biomarkers such as circulating tumor DNA,circulating tumor cells,DNA methylation,metabolomics,and tumor-educated platelets.These approaches serve as important complements to tissue biopsy.Overall,repeated biopsy provides comprehensive insights into resistance mechanisms at both molecular and phenotypic levels,facilitating optimized therapeutic decision-making and advancing precision medicine in NSCLC.In the future,the combined application of tissue biopsy and liquid biopsy,together with advances in detection technology,is expected to further improve the level of individualized management and clinical benefits of NSCLC.
苗雨晴;蒋莉莉
610041 成都,四川大学华西医院 病理科610041 成都,四川大学华西医院 病理科
医药卫生
非小细胞肺癌重复活检耐药机制靶向治疗液体活检
Non-small cell lung cancerRepeated biopsyResistance mechanismsTargeted therapyLiquid biopsy
《肿瘤预防与治疗》 2026 (6)
486-495,10
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