PROJECT SUMMARY/ABSTRACT Minimally invasive liquid biopsies have revolutionized our understanding of cancer biology and emerged as biomarkers for disease monitoring and drug development. The practice of longitudinal sampling of cancer- derived material from blood, including Circulating Tumor Cells (CTCs) and circulating tumor DNA (ctDNA), has been limited to a few commercial entities or academic laboratories with the requisite technological capacity. The UWCCC Circulating Biomarker Core (CBC) was established in 2019, leveraging innovative technologies and clinical research infrastructure, to expand access to these biospecimens and assays for UWCCC members, and directly addresses UWCCC strategic plan A2.1. The CBC is structured to follow NCI guidance for biomarker development focusing on assay robustness, feasibility, and impact for exploratory, integrated, and integral biomarkers1. The CBC houses an expert research team and equipment to identify, organize, and process samples from patients on clinical trials, both at UWCCC, across the catchment, and from national consortia. Standard analytes purified range from plasma for ctDNA, cytokines, metabolites, and exosomes as well as nucleated cells for CTC analysis and immune cell studies. The analyses performed include rare cell phenotyping, gene expression profiling, and genetic analysis among others. The CBC coordinates with the Translational Science Biocore (TSB) Biobank and clinical Biospecimen Disease-Oriented Team (DOT) weekly to ensure efficient and timely processing of samples collected by these teams. In collaboration with the Wisconsin State Lab of Hygiene, the CBC now provides a pipeline to move promising liquid biomarkers towards CLIA-certification that can serve as an integral biomarker for clinical trials. One project, evaluating gene expression analysis of prostate cancer CTCs (UH2CA260389; Journal of Clinical Oncology2), has entered this pipeline and is being developed as an integral biomarker and clinical grade assay. The CBC provides researchers access to innovative technology to develop new biomarkers as well as test these biomarkers in clinical trials using established standard operating procedures (SOPs) for biospecimen processing and analysis. The CBC is led by expert faculty leaders including CBC Director Dr. Joshua Lang, UWCCC TM program co-leader, and Dr. Jennifer Schehr who has served as facility director for the CBC since its inception. Our Specific Aims are to 1) develop exploratory liquid biopsy of biomarkers to advance our understanding of cancer and treatment resistance; 2) perform clinical testing and translation of new liquid biopsy assays as integrated biomarkers, and 3) perform analytical validation in preparation for clinical diagnostic laboratory implementation as integrated and integral biomarkers. Over 2019-2021 as a developing core, CBC has had tremendous impact on UWCCC member research. Specifically, CBC collaborated with 46 unique users, of which 67% were UWCCC...