Targeting tumour vasculature: the development of combretastatin A4

被引:194
作者
Griggs, Jeremy [1 ]
Metcalfe, James C. [1 ]
Hesketh, Robin [1 ]
机构
[1] Univ Cambridge, Dept Biochem, Tennis Court Rd, Cambridge CB2 1QW, England
基金
英国生物技术与生命科学研究理事会;
关键词
D O I
10.1016/S1470-2045(00)00224-2
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The requirement for neovascularisation to permit the development of solid tumours beyond a threshold size, has focused attention on the therapeutic potential of agents that prevent angiogenesis. The multistep nature of angiogenesis presents several targets for intervention, including the inhibition of the endothelial-cell migration or proliferation normally associated with developing vessels. Compounds that damage established tumour vasculature are also of potential clinical use. We review the development of one such antivascular drug, combretastatin A4. This tubulin-binding agent was originally isolated from an African shrub, Combretum caffrum. The disodium combretastatin A4 phosphate prodrug is currently undergoing phase I clinical trials in the UK and USA. This review assesses the in vitro and in vivo data for combretastatin and the prodrug, and the preliminary data that have emerged from the phase I clinical trials.
引用
收藏
页码:82 / 87
页数:6
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