PROJECT SUMMARY/ABSTRACT The University of Wisconsin Carbone Cancer Center (UWCCC) seeks continued funding for years 49-53 to further accelerate its mission to dramatically reduce the burden of cancer within and beyond its catchment – the State of Wisconsin. The UWCCC, which is a matrix center within the University of Wisconsin School of Medicine and Public Health (SMPH), is composed of 218 faculty members from 38 departments and 9 schools of the University of Wisconsin-Madison (UW). Our members pursue cancer care, research, and education through 6 scientific programs (Human Cancer Virology, Cancer Genetic and Epigenetic Mechanisms, Tumor Microenvironment, Imaging and Radiation Sciences, Developmental Therapeutics, and Cancer Prevention and Control) supported by 12 Shared Resources. During the current grant period (2017-2021), leadership has successfully recruited >40 new and more diverse members and strengthened existing or new infrastructure facilitating our membership publishing 3,351 cancer-relevant manuscripts (31% inter- or intra-programmatic, 53% inter-institutional) with a significant increased proportion in high (≥10) impact factor journals (prior grant, 11% compared to current 23%), increasing our NCI research (Direct 2017 $18.6M, 2021 $24.9M) and total research funding (Direct 2017 $70.4M, 2021 $76.3M), obtaining more multi-project awards (P, U), supporting more trainees and supporting communities throughout our expanded catchment. The UWCCC will accomplish this mission through nurturing a diverse and supportive cancer community, reliable infrastructure, and efficient resources. The UWCCC worked to decrease the burden of cancer in our catchment and beyond through prioritized research areas (e.g., innovative therapies and biomarkers, cancer imaging, and expanded population-based cancer research), enhanced research platforms (e.g., improved clinical research infrastructure and shared resources), increased efforts to build mission-related philanthropy, and expanded local- to-global partnerships.