Endothelial cell effects of cytotoxics: balance between desired and unwanted effects

被引:46
作者
de Vos, FYFL [1 ]
Willemse, PHB [1 ]
de Vries, EGE [1 ]
Gietema, JA [1 ]
机构
[1] Univ Groningen Hosp, Div Med Oncol, Dept Internal Med, NL-9700 RB Groningen, Netherlands
关键词
Accidental angiogenesis; Metronomic" chemotherapy; vascular toxicity; endothelial damage; angiogenesis inhibitors;
D O I
10.1016/j.ctrv.2004.05.003
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Since Folkman defined angiogenesis more than 25 years ago as the most important process in tumour growth and metastasis, specific anti-angiogenic agents have been developed. One obvious route to block this process was until recently overlooked, however. Tumour endothelial cells are different from normal endothelial cells and may respond differently to conventional cytotoxics. Chemotherapeutic-induced vascular toxicity has been observed in various clinical studies and seems to be based on endothelial cell damage as seen in vitro in human umbilical vein endothelial cells (HUVEC) models with protracted low-dose cytostatic exposure. Translated into the clinical setting, such "metronomically" administered chemotherapy could lead to anti-angiogenesis enhancing anti-tumour efficacy of cytostatic drugs. This paper reviews the desired anti-tumour endothelial activity versus the unwanted general vascular toxicity of cytostatic drugs. Several ways to enhance the anti-tumour activity and to circumvent the unwanted vascular toxicity of these "accidental" anti-angiogenic drugs will be discussed. (C) 2004 Elsevier Ltd. All rights reserved.
引用
收藏
页码:495 / 513
页数:19
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