Because angiogenesis is necessary for tumor growth, inhibition of blood vessel formation is an excellent target for cancer therapy. The inherent complexities of current animal models, however, complicate screening of compounds for anti-angiogenic activity. In Phase I research, zebrafish (Danio rerio) embryos will be used to develop a rapid whole animal assay for screening potential drug candidates for anti-angiogenic activity. The inherent advantages of the zebrafish make it highly suitable for use for drug screening. Zebrafish embryos can be generated and maintained inexpensively and are amenable to automated analysis. Introduction of drugs into the embryo is simple. Because the embryos are transparent, drug and toxicity effects can be easily detected. Following staining, blood vessels and organs can be examined under the microscope without further sample preparation. Rapid embryonic development also facilitates rapid detection of drug effects. The zebrafish is particularly well suited for screening of potential inhibitors of angiogenesis because blood vessel patterning is highly characteristic in the developing embryo. Preliminary studies indicate that chemicals introduced into the developing embryo induce observable, dose-dependent responses. Phase I research will compare results obtained using the zebrafish model with other vertebrate models.
By providing a rapid, high throughput, automated method for screening drugs, the zebrafish assay will help to streamline flee drug development process for cancer and heart disease. In 1997 the worldwide market for drug screens for cancer and heart disease was $500M.
