Project Summary Since the last competitive review of this Cancer Center Support Grant (CCSG) in 2012, the NCI-designated Perlmutter Cancer Center (PCC), previously NYU Cancer Institute, has weathered the devastation of Superstorm Sandy and emerged into a period of profound transformation and expansion. Propelled by a transformative gift from Laurie and Isaac Perlmutter, renewed and enhanced institutional support from the NYU Langone Health system (NYULH) and a new Director, we have overhauled our leadership team, expanded our clinical and research facilities, and developed a new strategic vision and began implementing a new Strategic Plan. Guided by this plan, our Scientific Programs and Shared Resources have been restructured, and we embarked on a major recruitment campaign that has yielded 12 additional new leadership and/or senior faculty recruits, 15 other new cancer center faculty recruits, and 68 new members overall. Under revised, more stringent criteria, membership has been streamlined to 180 full members and 56 associate members. Members carry out research as part of 5 Scientific Programs, Cancer Genome Dynamics, Cancer Cell Biology, Tumor Immunology, Melanoma, or Epidemiology and Cancer Control, assisted by 10 Shared Resources and 2 Developing Shared Resources. Our clinical trials office has been reorganized and substantially expanded under new leadership and a new Phase I unit has opened. Subsequently, trial availability, quality, and accrual have increased, while the time to trial opening has been markedly reduced. In line with our increased geographic scope and patient population, we have redefined and enlarged our catchment area. Aided by the creation of a new Department of Population Health at NYU Langone School of Medicine and the College of Global Public Health at the NYU main campus, our Population Sciences research has increased in breadth and quality. Most importantly, our laboratory scientists have made paradigm-shifting discoveries, our clinicians have led multiple practice-changing trials, and our population scientists have yielded new insights into the causes of cancer and how to control the disease, contributed to major public health policy changes and initiatives, and established new community outreach programs that address the specific cancer burdens and health disparities in our catchment area. Although PCC is located in a city with four other NCI-designated cancer centers, our catchment area differs substantially from the others: we are the major provider to lower Manhattan, and have expanded into Brooklyn, the largest and fastest growing borough in New York City, as well as to Queens and Long Island.