This long-standing training program, currently in its 29th year of NRSA support, is centered on the educational and advanced research functions of the program of Molecular Pharmacology and Cancer Therapeutics (MPCT) in the State University of New York at Buffalo (SUNYAB), Roswell Park Graduate Division. The MPCT Program and the NRSA supporting it have traditionally focused on the training of predoctoral students. It reflects the activities of 27 senior faculty of the Grace Cancer Drug Center (GCDC), 1 emeritus faculty member, and 2 faculty members who belong to other research units. Program faculty have diverse backgrounds and research interests with a common focus on exploiting recent advances in the molecular characterization of cancer for the development of new approaches to treatment and prevention. Research activities of the program can be broadly classified into molecular target discovery, mechanisms of drug action and resistance, prevention, and therapeutic development. The MPCT program is unique because it provides trainees with a broad perspective on cancer related issues including cancer incidence and survival, the spectrum of scientific approaches to cancer, the importance of interactions between basic and clinical researchers, and the realities of patient care. Further, trainees are exposed to cutting edge research at each stage of the cancer drug development process, from the laboratory bench to the hospital bedside. This is accomplished by integrating an academic program comprised of a diverse faculty within the setting of a world-renowned, NCI-designated, Comprehensive Cancer Center. The training opportunities offered are supplemented by integration with collaborative studies carried out by Program faculty and colleagues at Roswell Park Cancer Institute (RPCI) and the SUNYAB. Predoctoral students in the MPCT program (average 5.2/entering per yr;30 currently enrolled;18 of the 30 have or will receive support from the currently active NRSA) are drawn from excellent national and international institutions. These graduate students have Bachelor's or Master's degrees in the physical or biological sciences, or have M.D. degrees. This application proposes support for 5 predoctoral trainees (6 currently supported with CURE supplement). The labs of the GCDC occupy a six story building (49,655 square feet net lab space) on the campus of RPCI. The labs, half of which are newly remodeled, are equipped with modem instrumentation appropriate to the training proposed. In addition to the GCDC, trainees have access to research programs in the areas of immunology, cancer genetics, molecular and cellular biology, cancer prevention, molecular and cellular biophysics as well as RPCI clinical units. Trainee research is facilitated daily RPCI core facilities supported by the Comprehensive Cancer Center Grant and the facilities of SUNYAB.