ABSTRACT, Overview and Essential Characteristics The Indiana University Melvin and Bren Simon Comprehensive Cancer Center (IUSCCC) is Indiana's only NCI- designated Comprehensive Cancer Center and is dedicated to cancer research, education, and patient care for the residents of Indiana and beyond. Our Vision is that Research Cures Cancer, and our Mission is to create an expanding community of researchers and health professionals who conduct outstanding research, provide excellence in education, and deliver high-quality patient-centered care. IUSCCC received an overall score of “Outstanding” at the last (2018) renewal and achieved Comprehensive status. In the current grant period, IUSCCC has continued to build on this exceptional foundation of accomplishment. Compared to 2018, there has been a 24% increase in peer-reviewed funding (17% increase in NCI funding), 53% increase in Team Science MPI grants, 36% increase in publications (20% in journals with IF>10), and 27% increase in accrual to therapeutic investigator-initiated trials. With the recruitment of Dr. Kelvin Lee as the third IUSCCC Director in February 2021, there has been major alignment and integration of IUSCCC's oversight of the strategic direction in cancer service line efforts (quality and clinical pathways) with research and education across both the IU School of Medicine and the IU Health health care system. IUSCCC's expertise was recently recognized by being named a member of the National Comprehensive Cancer Network. We have strategically and substantially increased our translational research expertise and capabilities, including the development of the Cancer Drug Discovery & Development Accelerator, Brown Center for Immunotherapy, and Early Phase Clinical Trial Program. Our global oncology efforts continue to grow with establishment of the Center for Global Oncology and Health Equity. We launched the new Translational Cancer Biology PhD program based in IUSCCC. We have significantly expanded the Office of Community Outreach and Engagement and its activities, and elevated the importance of diversity, equity, and inclusion (DEI) with creation of an Associate Director for DEI in 2021. IUSCCC seeks to continue its upward trajectory by enabling paradigm-practice-policy-changing research through: 1) providing foundational organizing capabilities in research infrastructure and shared resources; physical space; institutional alignment, integration, and resources; transdisciplinary collaboration; DEI; and programmatic and administrative leadership; 2) developing efforts in education, data, informatics, biostatistics, and community outreach and engagement that integrate internal activities and meaningfully engage our external communities and partners; 3) fostering cancer- focused research in mechanism-based biology and medicine, BenchBedsideMain Street translational research, and population health/social determinants research that have significant local and global impact; and 4) trainin...