抗血管生成靶向药物治疗肿瘤引起高血压的机制及研究进展

摘要

血管生成对肿瘤的发生发展起着重要的作用,抗血管生成肿瘤治疗逐渐成为一种有前景的肿瘤治疗方法.血管内皮生长因子(VEGF)因其在血管生成过程中的关键作用成为了一个重要的治疗靶点.多种以VEGF及其通路为靶点的药物已经在临床中广泛用于结肠癌、非小细胞肺癌、晚期肾癌、肝癌、乳腺癌的治疗.高血压是VEGF抑制剂最常见的心血管副作用,但其引起高血压的具体分子机制尚不明确,与之相关的有内皮功能紊乱、NO释放减少、微血管网稀疏、内皮素 -1水平的上调等.本文着重讨论 VEGF作为抗血管生成靶点的肿瘤治疗作用、VEGF抑制剂引起高血压的分子机制以及此类药物引起高血压的治疗策略.%Angiogenesis is critical to the growth of human tumors and the development of metastasis,and antiangio-genic therapy has emerged as an important concept in the treatment of solid tumors.Vascular endothelial growth factor (VEGF)represents an important therapeutic target,as it is the primary mediator of angiogenesis.Various therapeutic agents targeting the VEGF pathway have been now widely used in the treatment of patients with colorectal,non-small-cell lung,advanced renal cell,hepatocellular,and breast cancer.One of the most commonly observed side effects of inhibition of VEGF signaling is hypertension.Molecular mechanisms underlying VEGFI -induced hypertension are unclear,but endothelial dysfunction and increased vascular resistance,due to impaired nitric oxide signalling,micro-vascular rarefaction and endothelin-1(ET-1)upregulation have been implicated.We focus on VEGF as a target for antiangiogenesis and how this affects increased blood pressure.Putative mechanisms underlying VEGFI-induced hypertension are highlighted and therapeutic strategies to manage such hypertension are discussed.