摘要
目的系统总结乳腺癌靶向药物治疗的类型及耐药机制,并探讨优化治疗策略的未来发展方向。方法对近年来国内外有关乳腺癌靶向药物治疗研究的文献进行综述。结果靶向药物分类主要包括人表皮生长因子受体2(human epidermal growth factor receptor 2,HER2)抑制剂、CDK4/6抑制剂、磷脂酰肌醇3激酶(phosphatidylinositol 3-kinase,PI3K)/蛋白激酶B(protein kinase B,PKB/AKT)/雷帕霉素机制靶标(mechanistic target of rapamycin,mTOR)通路抑制剂、聚腺苷二磷酸核糖聚合酶抑制剂、免疫检查点抑制剂等,HER2抑制剂显著改善HER2阳性乳腺癌患者生存、CDK4/6抑制剂延长激素受体阳性患者无进展生存期,聚腺苷二磷酸核糖聚合酶抑制剂对BRCA突变患者有效;耐药机制核心包括靶点变异、PI3K/AKT/mTOR等补偿通路激活、表观遗传失调、ATP结合盒转运蛋白介导的药物外排等;双靶向联合(如曲妥珠单抗+帕妥珠单抗)、液体活检动态监测耐药基因突变、表观遗传调节剂等可部分逆转耐药。结论耐药性是限制乳腺癌靶向药物治疗长期获益的关键瓶颈,未来需通过多组学整合以解析肿瘤异质性,结合多靶点抑制、实时监测、多维度干预策略,运用人工智能预测耐药演变,突破耐药困境,以发展个体化联合治疗策略以提升患者生存质量。
Objective To systematically elucidate the resistance mechanism of targeted drug therapy for breast cancer and to discuss future direction of optimized treatment strategies.Method A literature review on targeted therapy for breast cancer had been conducted based on recent domestic and international research.Results Contemporary breast cancer targeted therapies mainly comprised human epidermal growth factor receptor 2(HER2)-directed agents,CDK4/6 inhibitors,phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin pathway blockers,poly(ADP-ribose)polymerase inhibitors,and immune checkpoint modulators,etc.While these agents had conferred subtype-specific survival benefits,resistance developed through target mutations,compensatory signaling,epigenetic alterations,drug efflux pumps,among other mechanisms.Emerging strategies for reversing drug resistance included dual-targeted approaches(such as trastuzumab in combination with pertuzumab),dynamic monitoring of drug-resistant gene mutations by liquid biopsy,epigenetic modulators,etc.Conclusions Drug resistance remains a key bottleneck limiting long-term efficacy of breast cancer targeted therapy.Future research should integrate multi-omics approaches to decipher tumor heterogeneity,implement combinatorial multi-target inhibition with real-time monitoring of multidimensional interventions,and leverage artificial intelligence to predict resistance evolution.This integrated strategy is expected to enable personalized combination therapies,ultimately overcoming drug resistance and improving patient survival outcomes.
作者
袁双龙
贾立周
周毅
YUAN Shuanglong;JIA Lizhou;ZHOU Yi(Department of Thyroid and Breast Surgery,Bayannur Hospital,Bayannur,Inner Mongolia 015000,P.R.China;Central Laboratory,Bayannur Hospital,Bayannur,Inner Mongolia 015000,P.R.China;Department of Breast Surgery,The First Affiliated Hospital of Harbin Medical University,Harbin 150001,P.R.China)
出处
《中国普外基础与临床杂志》
2025年第9期1181-1188,共8页
Chinese Journal of Bases and Clinics In General Surgery
关键词
靶向药物治疗
耐药机制
乳腺癌
治疗策略
targeted therapy drugs
drug resistance mechanism
breast cancer
treatment strategy
作者简介
通信作者:周毅,Email:lubj2001@163.com。
