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抗血管生成药物:癌症治疗的当前认知与新方法

Antiangiogenic drugs: current knowledge and new approaches to cancer therapy.

作者信息

Mauriz Jose L, González-Gallego Javier

机构信息

Ciberehd and Institute of Biomedicine, University of León, Campus of Vegazana, s/n, 24071 León, Spain.

出版信息

J Pharm Sci. 2008 Oct;97(10):4129-54. doi: 10.1002/jps.21286.

Abstract

Angiogenesis--process of new blood-vessel growth from existing vasculature--is an integral part of both normal developmental processes and numerous pathologies such as cancer, ischemic diseases and chronic inflammation. Angiogenesis plays a crucial role facilitating tumour growth and the metastatic process, and it is the result of a dynamic balance between proangiogenic and antiangiogenic factors. The potential to block tumour growth and metastases by angiogenesis inhibition represents an intriguing approach to the cancer treatment. Angiogenesis continues to be a topic of major scientific interest; and there are currently more antiangiogenic drugs in cancer clinical trials than those that fit into any other mechanistic category. Based on preclinical studies, researchers believe that targeting the blood vessels which support tumour growth could help treatment of a broad range of cancers. Angiogenic factors or their receptors, endothelial cell proliferation, matrix metalloproteinases or endothelial cell adhesion, are the main targets of an increasing number of clinical trials approved to test the tolerance and therapeutic efficacy of antiangiogenic agents. Unfortunately, contrary to initial expectations, it has been described that antiangiogenic treatment can cause different toxicities in cancer patients. The purpose of this article is to provide an overview of current attempts to inhibit tumour angiogenesis for cancer therapy.

摘要

血管生成——即从现有脉管系统生成新血管的过程——是正常发育过程以及众多病症(如癌症、缺血性疾病和慢性炎症)不可或缺的一部分。血管生成在促进肿瘤生长和转移过程中起着关键作用,它是促血管生成因子和抗血管生成因子之间动态平衡的结果。通过抑制血管生成来阻断肿瘤生长和转移的潜力为癌症治疗提供了一种引人入胜的方法。血管生成仍然是主要的科学研究热点;目前在癌症临床试验中的抗血管生成药物比其他任何作用机制类别的药物都要多。基于临床前研究,研究人员认为,靶向支持肿瘤生长的血管有助于治疗多种癌症。血管生成因子或其受体、内皮细胞增殖、基质金属蛋白酶或内皮细胞黏附,是越来越多已获批的临床试验的主要靶点,这些试验旨在测试抗血管生成药物的耐受性和治疗效果。不幸的是,与最初的预期相反,已有研究表明抗血管生成治疗会在癌症患者中引发不同的毒性。本文旨在概述目前为癌症治疗抑制肿瘤血管生成的尝试。

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