Although knowledge of cancer biology in the laboratory has increased exponentially in recent years, progress in cancer treatment in the clinic has been more gradual. To accelerate progress in the clinic, a larger group of exceptional clinician-investigators is needed to perform patient-oriented, hypothesis-driven therapeutic translational research. The MD Anderson (MDACC) K12 Paul Calabresi Program in Clinical Oncology has taken advantage of an extraordinary environment for clinical and translational research to help to fill this need. MDACC brings together 1,685 faculty and 40,000 new patients each year with a well-developed infrastructure for clinical and laboratory research and novel ideas that are supported by 188 NCI grants. For seven decades, MDACC investigators have made important contributions to clinical cancer research. Since the inception of the MDACC K12 Program in 2000, 23 junior-faculty investigators have been trained in patient-based translational research with the program's support. Currently, four faculty scholars are being trained in this program. All 18 of our graduates have become highly-productive clinician-scientists with 17 of 18 in full-time research. Four scholars have earned an M.S. or Ph.D. and three are pursuing a degree. Collectively, Calabresi Scholars have authored 397 peer-reviewed publications while participating in the program and 967 following graduation with impact factor >5 in 40.6% and >10 in 10.9%. They have competed successfully for $32.4M in grants and contracts. Over the next 5 years, faculty supported by this award will conduct hypothesis-driven clinical trials and will have the opportunity to earn an M.S. or Ph.D. in a newly-chartered program in Clinical and Translational Science. They will participate in a new monthly Master Class and a new annual Calabresi Symposium. Their Individualized Training Plans will include didactic classes, clinical trials, publications, grant applications, and long-range planning. Each Calabresi Scholar is guided by a clinical mentor and a translational mentor chosen from 36 experts in clinical, laboratory, and translational research. Particular emphasis will be placed on rigorous evaluation and recruitment of minority scholars. Two new minority scholars have already been recruited. Our overall goal is to identify and develop careers of leaders who are needed to move an increasing number of new drugs and strategies from the laboratory to the clinic and to bring insights, images, data and tissue from the clinic to the laboratory, accelerating the development of more effective, less toxic personalized therapy. Funds are requested to include five junior faculty not only from MDACC, but also from the Baylor College of Medicine and UT Health in Houston.