) The goal of this revised K24 program is to allow the principal investigator to mentor fellows in translational research. In this revision we believe we have clarified the the extent and environment of our mentoring program for fellows, residents and medical students and how our clinical time is being modified to meet this expanding role. The revision has also expanded the description of the clinical research program. The PI's current program identifies new drugs that enhance the induction of apoptosis by chemotherapy. These clinical observations lead directly into clinical trials. The program is based on published laboratory studies showing that protein kinase C (PKC) and cyclin dependent kinase (CDK) inhibitors enhance the induction of apoptosis by chemotherapy in human gastric, breast, and colon cancer cell lines. These studies have already resulted in Phase I clinical trials including sequential paclitaxel followed by flavopiridol and paclitaxel followed by bryostatin-l. Numerous other preclinical observations are being considered for translation into clinical trials. In fact, based on our laboratory data, the clinical trials of UCN-01 and 5-Fu are now open. In addition, five letters of intent are now in place at the NCI with new drug combinations to perform additional clinical trials. To support this effort the PI has received a National Cancer Institute Grant R01CA67819, entitled """"""""Protein Kinase C: A Novel Target for Cancer Therapy."""""""" In addition to this support, the Center has provided supplemental support to his laboratory and clinical work. The career plan presented here represents a direct connection between the laboratory and a new therapeutic approach in cancer therapy. The mentoring of clinical oncology fellows and medical house staff is a critical part of this clinical/translational research program. My role as mentor begins with fellows learning how to design, conduct and analyze phase I and II clinical trials. Education in clinical trial methodology is given by direct supervision and teaching on a one-to-one basis through tutoring and in conference. The fellows with the Principal Investigator write the protocol, follow the study through review, treat patients on the study, manage the data, monitor response and toxicity, and repeal results. The fellows oversee treatment of patients on the clinical trials under my direct supervision. As informed consent is of critical importance in clinical research, the fellows are carefully instructed and supervised in writing the consent form. At the appropriate time, the fellows organize, analyze and interpret data for presentation at national meetings. A clinical investigator trained in translational research, who can see its evolution from the benchtop to the clinic, is of paramount importance to the future of medical oncology. This K24 award mechanism represents the essence of what we are proposing and for which support is needed.
