There is a long history of oral cancer research in the Chicago area. In this application, the University of Chicago and Northwestern University are combining their efforts in laboratory and clinical sciences to foster interactions between laboratory scientists and clinical investigators, to generate new treatment hypothesis and conduct translational research in oral cancer. We will seek to optimize currently available therapy and improve the rehabilitation of the oral cancer patient. Our long-term goals are to identify new approaches to early diagnosis and more successful therapy based on an understanding of the molecular mechanisms underlying this disease. We will support pilot projects and the rapid generation of new clinical laboratory hypotheses utilizing developmental research funds provided by the grant and supplemented by the participating institutions and provide education and training in oral cancer research for basic and clinical investigators. The principal investigators have a long history of collaboration and have also conducted independent studies of oral carcinogenesis and cancer therapy and rehabilitation. Four projects are described in this application Project #1 will examine mechanisms underlying oral carcinogenesis that may identify tools for future early detection. Project #2 will study the role of apoptosis in oral carcinogenesis. Project #3 will study molecular pharmacokinetics of chemotherapy with concomitant radiotherapy in order to deliver more effective and less toxic therapy. Project #4 will measure organ function and rehabilitation in patients treated with curative intent chemoradiotherapy. Three pilot projects are also included which will be funded by the grant and matching funds made available by the two participating institutions. These activities will be supported by three cores. The administrative core, the biostatistical, data management and clinical core, and the tissue procurement and laboratory core. Core A, the administrative core will monitor ongoing projects, assure successful and timely performance of scientific tasks and interact with the internal and external advisory boards. Core B, the biostatistical data management and clinical core will provide expertise in data collection and analysis. Core C, the laboratory core will be responsible for the appropriate collection, preparation and distribution of human tissues required for ongoing projects.