Project Summary 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 1,743 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 378 NCI grants. For eight decades, MDACC investigators have made important contributions to clinical cancer research. Since the inception of the MDACC K12 Program in 2000, 35 junior-faculty investigators have been trained in patient-based translational research with the program's support. Of the 31 graduates, 28 (89%) remain in academia and 13 have led or contributed to discoveries that have changed the standard of cancer care. Among the 12 scholars trained since the last renewal, three are from under-represented minorities (URMs). During the current grant period, eleven of twelve (91%) scholars had either earned an additional advanced degree during the program or had previously earned an MS or PhD. Collectively, Calabresi Scholars have authored 485 peer-reviewed publications while participating in the program and 1,844 following graduation with impact factor >5 in 28.6% and >10 in 11.6%. They have competed successfully for $35M 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 track in Clinical and Translational Science. They will participate in the monthly “Master Class” and the annual “Calabresi K 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 40 experts in clinical, laboratory, and translational research. Particular emphasis will be placed on rigorous evaluation and recruitment of minority scholars. 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 Baylor College of Medicine and UT Health in Houston.