Cancer is a growing problem in this country and in the world. It is the second leading cause of death in this country, accounting for nearly one in four deaths. In addition to the human costs, the National Institutes of Health estimate that cancer is estimated to cost this country nearly $200 billion in direct and indirect costs. Not surprisingly, cancer also represents the largest current effort in pharmaceutical companies based on the number of drugs in development. Yet, despite strong successes in recent decades in understanding the molecular basis of many cancers and cancer syndromes, overall five year survival rates for all cancers has changed very little over the past three decades. Furthermore, most cancers are treated in a manner little changed over this period. Therefore, cancer represents a large market with a substantial unmet need. The difficulties in identifying effective treatments lie primarily in the difficulties inherent in targeting tumor cells but also in the reliance on useful but limited models such as cell culture. These sorts of models fail to assess tumors in situ. Especially in cancer, whole animal approaches ensures better efficacy and also addresses toxicity, the major stumbling block of most cancer treatments. However, whole animal screening in mammals is not practical due to the immense cost and time required. This Proposal focuses on a novel approach by Medros, founded on a proprietary platform optimized for high-throughput drug screening. The approach has been validated: the Medros platform provided the sole in situ, whole animal data for a drug now in Phase II clinical trials for Medullary Thyroid Carcinoma. This Proposal contains two aims. First, the laboratories of Dr. Cagan and Dr. Baranski will optimize a novel whole animal model for metastasis. The goal is to create a platform to identify lead compounds that will reduce the risk of the most dangerous aspect for most solid tumors: tumor cell migration and metastasis. In the second aim, Medros will use an existing Csk/Src platform to screen two focused drug libraries assembled by Tripos, an expert in drug libraries and screening. The larger goal of this Phase I proposal is to combine the academic skills of Drs. Cagan and Baranski for generating Drosophila cancer models with the screening skills and proprietary platform of Medros. The result is to leverage the advantages of a novel screening platform in the large and growing cancer market. ? ? ?
