This K24 grant application seeks to renew support for the principal investigator to conduct and to mentor trainees in the conduct of patient-oriented clinical research bridging early phase clinical trials with laboratory correlative studies. Key accomplishments made possible by this grant over the past 5 years include, 1) shifting the sources of my research funding from 100% industry and institutional support in 1998 to 85% NTH and 15% industry in 2003; 2) doubling the research activities of the Phase I Program at Vanderbilt, culminating in the award of a Phase I U01 cooperative agreement from NCI in March, 2003; 3) leading a national Phase II trial correlating biological changes in the EGFR signaling pathway in pre- and post-tumor biopsies with clinical outcome in 115 patients with metastatic colorectal cancer treated with gefitinib; 4) leading the clinical-translational research effort in the Vanderbilt SPORE in Gastrointestinal Cancer P50 grant funded by NCI September, 2002; 5) serving on the faculty of national programs designed to foster the careers of young investigators interested in careers in clinical-translational research including the ASCO/AACR Workshop on Methods in Clinical Cancer Research, the Amgen Fellows Alliance, and the Fellows Educational Session of the ASCO annual meeting; and 6) teaching and mentoring fellows and junior faculty at Vanderbilt who have gone on to careers in patient-oriented clinical research. These achievements attest to both the success of the K24 grant mechanism and to my abilities to apply the support from this grant in a fashion consistent with its intended uses. Although much has been accomplished, there is still much to do. I believe that continued support through this K24 award will be essential in my efforts to, 1) perform integrated laboratory-clinical studies that incorporate new technologies, including pharmacogenetic, pharmacogenomic, rumor genomic, and proteomic characterization as part of early phase clinical evaluation of new anticancer agents; 2) to continue to train young investigators to become translational researchers in early phase drug development; and 3) allow the principal investigator sufficient protected time to continue to expand educational activities related to patient-oriented clinical research.