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Mol. Hum. Reprod. Advance Access originally published online on April 22, 2008
Molecular Human Reproduction 2008 14(5):259-268; doi:10.1093/molehr/gan019
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© The Author 2008. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Antiangiogenic and vascular-disrupting agents in endometriosis: pitfalls and promises

Anne Van Langendonckt1, Jacques Donnez1,4, Sylvie Defrère1, Gerard A.J. Dunselman2 and Patrick G. Groothuis3

1Department of Gynaecology, Université Catholique de Louvain, Avenue Hippocrate 10, 1200 Brussels, Belgium 2 Research Institute GROW, Department of Obstetrics and Gynaecology, University Hospital Maastricht, Maastricht, The Netherlands 3Organon Biosciences, Schering-Plough, P.O. Box 20 5340, BH, Oss, The Netherlands

4 Correspondence address. Tel: +32-2-764-95-01; Fax: +32-2-764-95-07; E-mail: donnez{at}gyne.ucl.be

It is widely known that angiogenesis plays a key role in endometriotic lesion formation and development. Antiangiogenic treatments aimed at inhibiting new vessel formation have proven efficient in experimental models. However, as antiangiogenic strategies do not target pre-existing pericyte-protected vessels, they require chronic administration and are likely to be beneficial for early-stage disease only or to prevent recurrence after surgery. Moreover, they may have detrimental effects on reproductive function. Vascular-disrupting agents (VDAs) have emerged as a promising new tool for the treatment of tumors. VDAs target established blood vessels, resulting in tumor ischemia and necrosis. These agents may therefore be more efficient against advanced disease. Two major types of VDAs are being developed for cancer: ligand-directed VDAs using antibodies, peptides and growth factors to deliver toxic effectors to tumor endothelium; and small-molecule VDAs exploiting physiological differences between tumor and normal endothelium to induce acute vascular shutdown. The ongoing evolution in genomics and proteomics is revolutionizing the discovery of novel endothelial markers. Several studies suggest that the vasculature of endometriotic lesions may have particular pathophysiological properties, which could be exploited for the development of selective VDAs. The aim of this review is to explore the merits and limitations of vascular therapy for the treatment of endometriosis.

Key words: endometriosis/angiogenesis/vascular-disrupting agent/antiangiogenic therapy/chronic inflammation

Submitted on February 12, 2008; resubmitted on April 9, 2008; accepted on April 15, 2008.


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