ABSTRACT – DIRECTORS OVERVIEW The O’Neal Comprehensive Cancer Center (O’Neal) at the University of Alabama at Birmingham is the only NCI- Designated Cancer Center in a four-state region including Alabama, Mississippi, Louisiana, and Arkansas. O’Neal’s catchment area is the State of Alabama, the state with the 8th highest cancer mortality in the country and a state with significant racial disparities in cancer incidence and mortality. More than half of the population is medically underserved, and 16 of the 67 Alabama counties are rural (RUCC 7-9). O’Neal (originally the UAB Comprehensive Cancer Center) was one of the first eight cancer centers designated by the NCI nearly five decades ago. O’Neal’s vision is Life without cancer. Our mission is to advance our understanding of cancer to improve prevention, detection, treatment, and survivorship for all people. A matrix Cancer Center, O’Neal has 187 members across 7 UAB Schools and 28 Departments. O’Neal members are supported by $22M of direct cost funding from the NCI and $59M in total direct cost cancer-relevant funding. Their research productivity led to 2,390 publications in the current CCSG cycle. O’Neal members are organized into 4 Research Programs: Cancer Biology and Immunology (CBI), Experimental Therapeutics (ET), Neuro-Oncology (NO), and Cancer Control and Population Science (CCPS). Program research is supported by 12 Shared Resources and is connected to 15 Disease Working Groups (DWGs) focused on translational clinical research and 8 Cancer Management Teams (CMTs) of the O’Neal Cancer Service Line (CSL) focused on multi-disciplinary cancer care. Programmatic Research is focused on seven cancers identified by the Office of Community Outreach and Engagement (COE) as being significant burdens to our catchment area communities. These include breast, colon, prostate, brain, lung, and cervical cancers, as well as multiple myeloma. COE provides cancer prevention, screening, and care education in most Alabama counties with a focus on the 26 counties with the greatest cancer burdens. During the current CCSG cycle, O’Neal members made significant contributions to our understanding of cancer that impacted treatment, including new approaches for treating brain cancers. In addition, improvements in O’Neal clinical trials processes and support lead to a 14% increase in accruals to therapeutic trials in 2020 over 2019 despite COVID-19, and a projected 21% increase in 2021. In addition, there was a 29% increase in NCI funding including two newly awarded NCI P01s, a $30M naming gift from O’Neal Industries, and initiation of a $300M project to build a new free-standing cancer hospital on the UAB Campus. Completion of the 2021-2026 O’Neal Strategic Plan revealed areas of basic, translational, and clinical excellence, including metabolism and obesity in cancer, cancer imaging, cancer immunology, cancer survivorship and increases in cancer care access to the underserved. This sets the stage for impactful scie...