The core mission of the Yale Cancer Center is to reduce suffering from cancer by being a global leader in cancer research, care and education. Designated as a Comprehensive Cancer Center in 1974, the past five years have been a period of significant growth and restructuring. Dr. Thomas Lynch became the 6th Director of the YCC in April 2009 and recruited more than 80 new basic, population, translational and clinical scientists. In addition to appointing a new Deputy Director, Dr. Daniel DiMaio, Senior Leadership and cancer Center Administration was completely redesigned. For this submission 6 of 7 Research Programs are under new leadership. During the most recent funding period, the YCCs 260 members published 2751 articles, (21% intra-programmatic and 14% inter-programmatic) and hold $93M in total cancer funding (including $29M from NCI). Accrual to therapeutic clinical trials more than doubled over the past year. Driven by remarkable institutional support, significant expansion during the prior funding period included building the $450M Smilow Cancer Hospital, opening 7 regional Care Centers in Southern CT and acquiring the former Hospital St. Raphael to create the nation's 4th largest hospital. This clinical care expansion was matched by establishing the Yale Cancer Biology Institute at Yale's West Campus. A detailed strategic planning process has begun with a resultant strong emphasis on optimizing our research programs and shared resources and investing in translational research, cancer genetics, and tumor immunology. This 5-year request is to support an organizational framework that promotes and fosters basic and translational cancer research. The 7 Research Programs include: Cancer Genetics and Genomics, Cancer Immunology, Cancer Prevention and Control, Developmental Therapeutics, Molecular Virology, Radiobiology and Radiotherapy and Signal Transduction. Support is requested for 8 Shared Resources including Yale Center for Genome Analysis, Flow Cytometry, Yale Pathology Tissue Services, Cesium Irradiator, Rapid Case Ascertainment, Yale Center for Molecular Discovery, Biostatistics and the Clinical Trials Office. To support center goals and objectives support for Senior Leadership, Planning and Evaluation, Administration, and Developmental Funds is also requested.