PROJECT SUMMARY The Fred & Pamela Buffett Cancer Center (Buffett Cancer Center or BCC), an NCI-designated Cancer Center since 1984, is committed to basic, translational, clinical and population science research, comprehensive educational programs, and outreach to underserved communities in our catchment area (Nebraska). The new BCC integrated cancer research and care facility increased Cancer Center-controlled research space 1.7-fold (total 400,000 sq ft), creating an environment which fosters scientific innovation and transdisciplinary collaborations. The Cancer Center is fully integrated into the university and its affiliated healthcare network, Nebraska Medicine (NM), with the Director reporting directly to the UNMC Chancellor and CEO NM and appointed BCC Physician-in-Chief. Two Cancer Center leadership positions were established since the last review, Deputy Director and Associate Director for Community Outreach and Engagement (COE), with the latter leading efforts to reduce cancer burden and disparities in diverse communities across Nebraska. The BCC also appointed four new senior leaders and eliminated dual leadership roles to promote clinical and translational research. The centralization, expansion and reorganization of the BCC Clinical Trials Office was completed and a new CTMS (OnCore) installed, culminating in a 1.8-fold increase in accrual to interventional clinical trials. Research infrastructure was enhanced by the addition of a new Preclinical Imaging Shared Resource as well as several new resources (e.g., Metabolomics, Organoids, Patient-Derived Models, Tissue Microarrays, Synthetic and Medicinal Chemistry, and Computational Chemistry). The BCC has three Research Programs: Cancer Biology Program (CBP); Targets, Modulators and Delivery Program (TMDP); and GI Cancer Program (GICP). Two programs, CBP and TMDP, changed names, reflecting the strategic realignment of their missions, themes and memberships. With 28 Members recruited during the current funding period, the BCC has a robust track record of clinical and translational research supported by 14 multidisciplinary awards (P01, P50, P20s, U awards; 6 from NCI) and 16 new MPI awards (11 from NCI). Cancer-relevant peer-reviewed research funding in the BCC increased 1.4-fold to $25.3M (Annual Direct Costs) and NCI funding increased 1.3-fold to $12.5 M (Annual Direct Costs) since our last review.