The development of new angiogenic inhibitors highlights a need for robust screening assays that adequately capture the complexity of vessel formation, and allow for the quantitative evaluation of the teratogenicity of new anti-angiogenic agents. This review discusses the use of screening assays in vertebrate embryos, specifically focusing upon chicken and zebrafish embryos, for the detection of anti-angiogenic agents.
Thalidomide is a teratogenic drug that caused horrific birth defects when prescribed as an antiemetic to pregnant women in the 1960's. The most stereotypical defect is symmetrical limb malformations such as phocomelia, though ear, eye and internal organ defects are also observed. Thalidomide was consequently withdrawn from the market. However, Thalidomide has since been shown to have many beneficial anti-inflammatory and immunomodulatory effects and is therefore used in a regulated manner in the treatment against cancers and inflammatory disorders. Sadly, new cases of babies affected by thalidomide are being born in Brazil, likely due to medicine sharing. The mechanisms of how thalidomide causes a wide range of embryonic malformations are becoming clearer; thalidomide is thought to act through molecules such as cereblon and tubulin and also affect blood vessel development and cell death, resulting in teratogenesis. Fully understanding the molecular events induced by thalidomide is essential if we are to develop a safe but clinically relevant form of the drug.
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