PROJECT SUMMARY/ABSTRACT Holden Comprehensive Cancer Center (HCCC) at the University of Iowa (UI) is the only NCI designated cancer center in the state of Iowa, a highly rural state that serves as the HCCC catchment area. The nearest Comprehensive Cancer Centers are approximately 200 miles away. The HCCC leverages its highly collaborative culture to advance transdisciplinary, collaborative cancer research that is particularly relevant to the people of Iowa. This includes basic cancer research, a strong portfolio of translational multi-investigator grants including two Specialized Program of Research Excellence (SPORE) P50 grants, a new NCI P01 and a growing portfolio of early phase clinical trials including studies based on basic science emerging from the HCCC. The HCCC functions administratively as a matrix Cancer Center with 170 Center members from seven UI colleges. Examples of transdisciplinary scientific advances include fundamental research into DNA repair, multiple promising early phase clinical trials based on laboratory advances made at the HCCC in the areas of toll-like receptor 9 (TLR9) agonists and pharmacologic doses of ascorbate, innovative studies in theranostics, and extensive molecular epidemiologic studies in lymphoma that have changed clinical practice. The members of the HCCC have $23.4 million in direct annual cancer-related, peer-reviewed, external research support. Of this, $11.0 million comes from the NCI. In the last funding cycle, HCCC members published 1,102 peer- reviewed cancer-relevant publications, with 76% involving intra-, inter-, or multi-institutional collaborations. The HCCC is organized into four research programs. Cancer Genes and Pathways (CGP) is the basic science program of the HCCC. Experimental Therapeutics (ET) and Free Radical Metabolism and Imaging (FRMI) are translational programs and Cancer Epidemiology and Population Science (CEPS) is a population science program. Support is requested for administration, evaluation and planning, clinical protocol development and monitoring, protocol review and monitoring and nine shared resources including Biostatistics, Central Microscopy, Flow Cytometry, Genomics, High Throughput Screening, Biospecimen Procurement & Molecular Epidemiology, Population Research, Radiation Free Radical Research and Viral Vector. The HCCC has a robust Community Outreach and Engagement effort focused on unique disparities in Iowa, such as rurality, obesity, HPV vaccination, that facilitates bidirectional interactions between the HCCC and the people of Iowa. It leverages the resources of the Iowa Cancer Consortium (ICC) and research infrastructure that extends into the community. It also has a comprehensive Career Enhancement (CE) Program. In summary, the HCCC provides a collaborative environment, infrastructure and resources to strengthen all aspects of interdisciplinary cancer research taking place at UI. The HCCC is requesting Cancer Center Support Grant (CCSG) funding and renewal o...