) The goal of this grant proposal is to allow the principal investigator to mentor and train new physician scientists within the framework of pursuing translational research. The environment created will be invaluable to developing independent investigators who can truly bridge the gap between basic science and clinical application of novel therapeutics. Because the principal investigator (PI) was recently appointed as Program Leader for the Gastrointestinal Tumor Program at the H. Lee Moffitt Cancer Center, he has the authority to restructure the program with a central focus on colorectal cancer and Src oncogenesis. With this focus, basic laboratory research projects are now directly linked to new clinical trials. The PI's research has recently identified the novel finding of mutations in the Src proto-oncogene in advanced human colorectal cancer patients which are activating and transforming. This observation provides the rationale for pursuing Src-directed novel therapeutic agents such as tyrosine kinase inhibitors and angiogenesis inhibitors for the treatment of colorectal cancer. To support this effort, the PI has recently received a renewal of his funding through the American Cancer Society as a Research project Grant (MPG 97751; 1/99 - 1/02) entitled """"""""Src Activation in Colon Cancer."""""""" We have several basic science collaborators who have provided us with a number of novel compounds which specifically inhibit Src or related tyrosine kinases in vitro and we are developing significant relationships with several pharmaceutical companies (Novartis, Zeneca, Sugen) which already have similar agents in the pipeline for clinical trials. The career plan presented in this application provides a direct relationship between the laboratory and the clinical application of novel therapeutics. The environment is ideal for the candidate interested in pursuing a career engaged in translational research. The surgical residency and the Society of Surgical Oncology approved surgical oncology fellowship will provide a continuous stream of candidates for this comprehensive laboratory and clinical research experience.
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