Using zebrafish (danio rerio), this SBIR proposal aims to develop an alternative whole animal model for assessing proliferation of human cancer cells and determining the effectiveness of potential drug candidates. The mouse is currently the model system of choice for assessing cell proliferation. Assay period, however, is typically 3-4 months because tumor development takes up to two weeks and animal survival times vary. To avoid cell rejection, Nude or SCID mice (immunosuppressed mice) are used; however, these mice are expensive to develop and maintain and are less hardy than normal mice. A further disadvantage of the mouse model is that a large number of cells per injection are required to generate a tumor. This requirement poses a problem because it is often difficult to procure large numbers of viable cells from primary tumors. In contrast, the zebrafish model requires only small numbers of cells for xenografting, and tumor formation and cell movement are easily monitored in the transparent embryo. Using cells from a variety of tissues, Phase I research will evaluate the utility of the zebrafish model for assaying cell proliferation. Using a panel of common chemotherapeutics, Phase I research will also assess its utility for drug screening.
By providing a rapid and inexpensive method for screening drug effects on cancer cell proliferation, the zebrafish assay will facilitate drug development of cancer therapeutics. The worldwide markets for drug screening is estimated at $700M.
