) The principal goal of this proposal is to increase the pool of clinical researchers who can conduct translational research studies in Gl Oncology and be able to devote more time to meritorious patient oriented research. The beginning clinical researchers will be mentored to develop patient-oriented research projects capitalizing on new, laboratory based chemotherapeutic treatment and prevention strategies for GI cancers. This proposal will demonstrate that the translational research program in Gl Oncology at USC has unique multidisciplinary interactions and collaborations providing the environment for an efficient mentoring program for beginning clinicians in patient oriented research. The translation research program in Gl Oncology is focusing on molecular determinants of clinical outcome, This program will not only lead to a better understanding of the spectrum of normal tissue toxicity for specific antineoplastic agents that target novel molecular pathways, but also provide a mechanistic evaluation of the effects of the agents on normal and tumor cells. These proposed projects will utilize: 1) the USC/Norris Comprehensive Cancer Center with its unique ethnically diverse patient population in Los Angeles County and the GCRC at the LAC-USC Medical Center; 2) the combined expertise of City of Hope Comprehensive Cancer Center (COH), USC and UC Davis Cancer Center in the areas of molecular pharmacology, pharmacokinetics, pharmacodynamics, cell cycle control and data acquisition to conduct innovative laboratory directed developmental studies supported by CTEP/NCI and 3) our close collaborations and access to clinical protocols from SWOG and CALGB. This proposal will feature three beginning clinicians responsible for three different patient oriented projects taking advantage of our successful program in molecular outcome research.