OVERALL PROJECT SUMMARY The Mayo Clinic Comprehensive Cancer Center (MCCCC) has engaged in intensive strategic planning and evaluation efforts, formed a new External Scientific Advisory Committee, and completed a significant transformation and reorganization with recruitment of new leaders and members to assure that prior concerns raised in the 2018 NCI review of the MCCCC NCI P30 Cancer Center Support Grant (P30CA015083) were fully addressed. With 3 highly integrated MCCCC sites serving distinct and diverse catchment areas (in Minnesota and the Upper Midwest, Arizona, and Florida), it is our intent to continue to be recognized as one of the finest NCI Designated Comprehensive Cancer Centers in the nation. In the last project period, MCCCC achieved its highest levels of annual cancer-relevant funding ($68.7M total peer-reviewed ($43.5M from NCI); $66M industry and non-peer reviewed; $23.4M state support) and accrual to cancer clinical trials (3,201 total interventional accruals with 1,829 interventional treatment accruals; 38,304 interventional accruals to population science studies; and 16,556 non-interventional accruals). Our Specific Aims are to: 1. Deeply engage the diverse patients and communities we serve at our three MCCCC sites and from across the nation and the globe, assuring that the research we conduct and the care we deliver meets patient and community priorities and needs and addresses the most important cancer challenges. 2. Conduct highly innovative, transformative, transdisciplinary research in our laboratory, clinical, and community settings and translate our discoveries to new means to prevent and treat cancer which yield new scientific paradigms, transform cancer practice, and impact cancer policy. 3. Test novel cancer diagnostic, prevention, detection, and therapeutic agents in clinical trials and interventions, engaging diverse patients and communities in our catchment areas and beyond. 4. Educate, train, and mentor a more diverse cancer workforce and leadership for the future, to meet the needs of those we serve, including the next generation of cancer investigators, physicians, scientists, and allied health personnel. 5. Overcome cancer health disparities, drive cancer health equity, and enhance inclusion and patient access through deep community engagement; the conduct of our research, training, and clinical care; development of innovative platforms and virtual and digital tools that transform cancer care delivery and decentralize cancer clinical trials and interventions to home and community settings; and sharing of our platforms, data, knowledge, and expertise. Through these aims we seek to honor the primary value of Mayo Clinic - the needs of the patient come first - and to ensure that we deliver the finest cancer care in the nation and the world derived from outstanding research, compassion, and constant innovation, bringing hope and healing to all of those we serve.