Tumours can adapt to anti-angiogenic therapy depending on the stromal context: lessons from endothelial cell biology.
It has long been recognized that interference with the blood supply of a tumour is an effective way to halt tumour progression, and even induce tumour regression. This can be accomplished by anti-angiogenic treatment which prevents the formation of a tumour neovasculature, or anti-vascular treatment, which aims at destruction of existent tumour vessels. The latter has received relatively little attention because there is a lack of specific tumour-endothelial markers. Instead, the current detailed knowledge on the factors and mechanisms, involved in angiogenesis, has enabled the development of a variety of angiogenesis inhibitors, especially those that target cellular signalling by vascular endothelial growth factor-A (VEGF-A), the most potent angiogenic factor known. These inhibitors have received lots of attention because they effectively inhibit tumour growth in pre-clinical models. However, in clinical trials these same inhibitors showed very poor anti-tumour activity. In this review we discuss this discrepancy, and we show that the tumour microenvironment is crucial to the sensitivity of tumours to anti-angiogenic therapy.
van Kempen
Léon C L
LC
Department of Pathology, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
Leenders
William P J
WP
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002450:Cell Communication; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009369:Neoplasms / Q000098:blood supply* / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000503:physiopathology; D015398:Signal Transduction / Q000187:drug effects; D017154:Stromal Cells / Q000187:drug effects / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000502:physiology
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D042461:Vascular Endothelial Growth Factor A