血管生成在恶性肿瘤中作用及靶向治疗策略的研究进展

Progress of angiogenesis and targeted therapy strategies in human cancer

大量研究表明,恶性肿瘤发生发展伴随着高水平的血管生成(angiogenesis)。血管生成过程极其复杂且所生成的血管结构具有特异性,在恶性肿瘤的增殖和侵袭转移过程中有十分重要的作用。血管生成信号通路的激活可增强肿瘤细胞的侵袭转移能力。本文总结了血管生成在恶性肿瘤中的作用,论述了恶性肿瘤血管生成相关的重要信号通路,分析了血管生成相关信号通路在恶性肿瘤中的多种调控机制,讨论了与此相关的抗VEGF/VEGFR信号通路的大分子单抗类药物、抗VEGFR等受体的小分子多靶点酪氨酸激酶抑制剂和抑制血管内皮细胞增殖迁移的重组人血管内皮抑制素等多种抗血管生成靶向药物,为进一步深入探究与血管生成相关的恶性肿瘤的靶向治疗提供参考。

Numerous studies have demonstrated that angiogenesis is a precondition of tumor development.Tumor angiogenesis is an extremely complex dynamic process,and there are significant differences in vascular structure.So angiogenesis plays a critical role in the proliferation,invasion and metastasis of malignant tumors.In this article,we review recent studies on the role of angiogenesis in human cancer,discuss the mechanisms of action of malignant tumor angiogenesis signaling pathways,and analyze various regulatory mechanisms of angiogenesisrelated signaling pathways in malignant tumors.According to the above signaling mechanisms,three types of antiangiogenesis targeted drugs are summarized,including macromolecular monoclonal antibodies of anti-VEGF/VEGFR signaling pathway,small molecule multi-target tyrosine kinase inhibitors against receptors such as VEGFR,and recombinant human endostatin inhibiting the proliferation and migration of vascular endothelial cells(ECs),providing a reference for further exploration of targeted therapy for malignant tumors related to angiogenesis.