Overall Project Summary / Abstract Now in its 22nd year of operation, Dana-Farber/Harvard Cancer Center (DF/HCC) was the first consortium model, NCI-designated Comprehensive Cancer Center. The consortium is comprised of 1,100 members from five principal Harvard-affiliated hospitals and two Harvard health science schools: Beth Israel Deaconess Medical Center (BIDMC), Boston Children’s Hospital (BCH), Brigham and Women’s Hospital (BWH), Dana- Farber Cancer Institute (DFCI), Harvard Medical School (HMS), Harvard T. H. Chan School of Public Health (HSPH), and Massachusetts General Hospital (MGH). Our overarching goals are to identify the genetic, biological, environmental, and behavioral bases of cancer and to develop effective strategies to reduce risk and improve preventive and treatment outcomes. Our catchment area is the Commonwealth of Massachusetts. Our steady progress over the last two decades has depended on the combined resources and talent at the 7 institutions; the unique consortium structure that enables collaborative bench-to-bedside translational research by population, basic, and clinical members; and well-coordinated Center leadership. DF/HCC embodies: 1) an integrated structure that aspires to excellence in research and accelerates clinically effective discoveries, 2) a cohesive research community for cross-institutional and transdisciplinary collaborations, and 3) a collectively large patient population that expedites the conduct of innovative clinical trials. Our work occurs in 18 Research Programs that cross scientific and institutional boundaries and span the gamut of population, basic, and clinical cancer research; members excel in each sphere. Two entities, a Center for Cancer Equity and Engagement (CCEE) and an Office for Cancer Research Education and Training (OCRET), help fulfill our responsibilities to the catchment area and to train future leaders in cancer research. The Center supports 14 Shared Resources that provide members with quality research services that cannot easily be duplicated in individual laboratories or institutions. A unified clinical research infrastructure serves all seven consortium institutions and makes it possible for members to conduct innovative early-phase (proof-of-concept and Phase I/II) clinical trials across the consortium. A portfolio of grants that transcend organizational and disciplinary boundaries (e.g., SPOREs, Program Projects, SU2C Dream Teams) reflect our collective translational and collaborative ideals. Our next phase of work is guided by a multi-part Strategic Plan that emphasizes mechanistic understanding of cancer, early cancer detection, equity, new therapeutic avenues, and a renewed commitment to education and mentorship. Underlying these goals are a culture and infrastructure streamlined for collaborative investigation of populations, fundamental cellular and molecular mechanisms, primary tumor specimens, and the barriers to improved cancer-related outcomes in all segments of ...