靶向血管治疗在乳腺癌精准治疗中的分子机制与临床应用OA
Molecular mechanisms and clinical applications of anti-angiogenic therapy in preci-sion treatment of breast cancer
肿瘤血管形成是乳腺癌进展与治疗应答的重要决定因素,本文首先回溯了肿瘤血管形成理论的提出与演变历程,系统梳理了其多样化的发生模式,包括出芽性血管生成、血管内生性分裂、血管拟态与血管共选等,深入剖析了不同模式的异质性特征及其在肿瘤进展各阶段的生物学意义.在分子调控机制层面,重点总结了缺氧诱导因子-1轴、血管内皮生长因子/血管内皮生长因子受体、血小板衍生生长因子/血小板衍生生长因子受体、血管生成素/血管生成素受体及Delta样配体4/Notch受体信号通路等核心调控网络的作用机制.此外,本文还全面回顾了抗血管生成治疗在乳腺癌中的临床探索历程,同时探讨了该治疗策略面临的疗效不稳定、耐药、缺乏精准分层标志物及治疗相关毒性等现实挑战.最后,本文提出了面向精准治疗的未来研究方向,包括优化血管正常化窗口、基于多维标志物的患者分层策略,以及利用空间组学解析肿瘤血管异质性等,为乳腺癌抗血管生成治疗的优化与创新提供了理论参考.
Tumor angiogenesis is a crucial determinant of breast cancer progression and therapeutic response.This review first traces the proposal and evolutionary course of the tumor angiogenesis theory,and systematically collates its diverse occurrence patterns,including sprouting angiogenesis,intussuscep-tive angiogenesis,vascular mimicry and vascular co-option,while conducting an in-depth analysis of the heterogeneous characteristics of different patterns and their biological significance at various stages of tumor progression.At the molecular regulatory mechanism level,this paper focuses on summarizing the mechanisms of core regulatory networks,such as the hypoxia-inducible factor-1 axis,vascular endothelial growth factor/vascular endothelial growth factor receptor,platelet-derived growth factor/platelet-derived growth factor receptor,angiopoietin/angiopoietin receptor,and Delta-like ligand 4/Notch receptor signa-ling pathway.In addition,this paper comprehensively reviews the clinical exploration of anti-angiogenic therapy for breast cancer,and discusses the practical challenges faced by this therapeutic strategy,inclu-ding unstable efficacy,drug resistance,the lack of precise stratification biomarkers and treatment-related toxicities.Finally,this paper proposes future research directions oriented toward precision therapy,inclu-ding optimizing the vascular normalization window,developing patient stratification strategies based on multidimensional biomarkers,and deciphering tumor vascular heterogeneity by using spatial omics.These findings provide a theoretical reference for the optimization and innovation of anti-angiogenic therapy for breast cancer.
王海;江一舟
复旦大学附属肿瘤医院乳腺外科,复旦大学上海医学院肿瘤学系,上海 200032复旦大学附属肿瘤医院乳腺外科,复旦大学上海医学院肿瘤学系,上海 200032
医药卫生
肿瘤血管形成乳腺癌抗血管生成治疗精准治疗
Tumor angiogenesisBreast cancerAnti-angiogenic therapyPrecision medicine
《北京大学学报(医学版)》 2026 (2)
251-256,6
国家自然科学基金(82403845)、全国博士后管理委员会博士后创新人才计划(A类)(BX20230092)、全国博士后管理委员会博士后面上项目(2025M772257)、上海市白玉兰浦江人才计划(24PJD019)、上海市自然科学项目(24ZR1413100)Supported by the National Natural Science Foundation of China(82403845)Postdoctoral Innovative Talents Support Program(Class A),National Postdoctoral Management Committee(BX20230092)General Program of China Postdoctoral Science Foundation,National Postdoctoral Management Committee(2025M772257)Shanghai Magnolia Pujiang Talent Program(24PJD019)Shanghai Natural Science Foundation Program(24ZR1413100)
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