肿瘤血管的靶向治疗研究进展  

Advances in targeted therapy for tumor vasculature

作　　者：陈瑶 陈梓琪 方坚鸿 CHEN Yao;CHEN Ziqi;FANG Jianhong(School of Pharmaceutical Sciences,Southern Medical University,Guangzhou 510515,China;Department of Hepatobiliary Surgery I,General Surgery Center,Zhujiang Hospital,Southern Medical University,Guangzhou 510515,China)

机构地区：[1]南方医科大学药学院,广东广州510515 [2]南方医科大学珠江医院肝胆一科,广东广州510280

出　　处：《广东医科大学学报》2025年第2期109-118,共10页Journal of Guangdong Medical University

基　　金：国家自然科学基金(82273313,82473996)。

摘　　要：肿瘤血管生成在肿瘤生长、侵袭和转移过程中发挥着关键作用。与正常血管相比,肿瘤血管在结构和功能上均表现出明显差异,如过度增殖、血流紊乱和渗透性增加等特征。基于这些特征,靶向肿瘤血管生成已成为抗肿瘤治疗的一个重要研究方向和治疗策略。以血管内皮生长因子/血管内皮生长因子受体(VEGF/VEGFR)为靶点的抗血管生成药物已在多种实体瘤中取得了显著疗效,但其临床应用仍面临有效率不高、耐药性和毒副作用等挑战。肿瘤血管不仅与肿瘤细胞相互作用,还通过重塑肿瘤微环境影响免疫细胞浸润和其他抗肿瘤药物的疗效。基于抗血管生成药物的联合治疗方案(如与免疫检查点抑制剂联用)已在临床中展现出显著疗效,进一步推动了这一领域的发展。血管正常化疗法作为一种新兴策略,通过改善肿瘤血管的结构和功能,为增强抗肿瘤治疗效果提供了新的思路。该文系统总结了肿瘤血管靶向疗法的发展历程,探讨现有抗血管生成治疗的局限性,特别是耐药性和有效率低等问题,并重点介绍了血管正常化疗法与基于抗血管的联合疗法的研究进展,探讨其在肿瘤治疗中的应用前景与挑战。Tumor angiogenesis plays a crucial role in tumor growth,invasion,and metastasis.Compared with normal vasculature,tumor blood vessels exhibit significant structural and functional abnormalities,such as excessive proliferation,disorganized blood flow,and increased permeability.Based on their function and these distinct features,targeting tumor angiogenesis has emerged as an important research direction and a therapeutic strategy in cancer treatment.Anti-angiogenic drugs targeting the VEGF/VEGFR axis have shown remarkable efficacy in various solid tumors;however,the clinical application of these agents is still challenged by issues such as suboptimal effectiveness,drug resistance,and adverse side effects.Recent studies indicate that tumor vasculature not only interacts directly with tumor cells but also remodels the tumor microenvironment,thereby affecting both immune cell infiltration and the therapeutic efficacy of other anticancer agents.Combination therapies,such as the integration of anti-angiogenic drugs with immune checkpoint inhibitors,have demonstrated significant clinical benefits,further advancing this field.Additionally,vascular normalization has emerged as a novel strategy that improves the structure and function of tumor blood vessels,offering new insights to enhance the efficacy of anticancer treatments.This review systematically summarizes the evolution of vascular-targeted therapies,discusses the limitations of current anti-angiogenic treatments(particularly in terms of resistance and limited efficacy),and highlights the progress in vascular normalization and combination therapy approaches.The prospects and challenges of these strategies in cancer treatment are also critically evaluated.

关 键 词：血管新生 抗血管生成药物 血管正常化 靶向 肿瘤血管生成治疗 

分 类 号：R730.5[医药卫生—肿瘤]