Abstract This Liquid Biopsy Research Laboratory (LBRL) will address specific unmet clinical needs in the early assessment of cancer by developing and validating multi-analyte liquid biopsy (LBx) technologies in distinct clinical contexts to maximize patient benefit by bringing together clinical, research, and industry experts. The LBRL proposed research is motivated by preliminary work published by us and others that indicate tumors leak detectable levels of multiple analytes, potentially early in tumor evolution, into the circulatory system. Here we propose three research projects that will address current clinical gaps in the early assessment of cancer using LBx technologies to maximally leverage resources toward gaining sufficient evidence for clinical implementation of at least one project by the end of the initial period. Clinical utilities will be explored in both screening and diagnostic workup in the early assessment of cancer with a focus on refining and validating technologies, methods, and assays for LBx and a particular emphasis on integrating the genomics and proteomics of single cells, as well as oncosomes, along with plasma genomics and proteomics to configure a final, clinically impactful assay. Aim 1 will focus on developing a comprehensive LBx-based companion to mammography for the early assessment of breast cancer (BC) with a focus on the `intent to treat' population of patients undergoing screening. Subaims include technology refinement for (1) a fit for purpose test consisting of previously validated immunofluorescence (IF) assays to characterize rare epithelial, endothelial, mesenchymal, and immune cells as well as oncosomes; and (2) existing comprehensive tests adapted for the requirements of low disease burden using multi-omic, multi-analyte approach for diagnostic workup following a positive mammogram or following a positive LBx screening test. Aim 2 will focus on developing enhanced screening and diagnostic workup for pancreatic cancer (PANC) through multi-omic capabilities on cells and plasma to create a multi-modal LBx aimed at a fit for purpose test appropriate as a screening tool prior to diagnostic imaging or an information-rich adjunct to an EUS procedure. Aim 3 is focused on the development of a PB LBx as a substitute to bone marrow aspirate (BMA) to diagnosed myeloma precursor states (MGUS and SMM) and detect the transition to multiple myeloma to easily identify candidates for early treatment intervention. The overall partnership team of the LBRL is leveraging established collaborations with a track record of identifying the clinical gap, designing studies that have a high likelihood of timely recruitment of patients and successful procurement of samples, technological innovation and refinement, compliant and scalable commercial solution development, and deployment into clinical care.

Project Narrative This Liquid Biopsy Research Laboratory (LBRL) partnership team, led by PI Peter Kuhn (academic) and Co-I Rick Wenstrup (industry) of Epic Sciences, is advancing biologically informed liquid biopsy (LBx) technology to fill gaps in current clinical practice of early cancer assessment. The three scenarios addressed by the LBx are 1) peripheral blood LBx as a companion to mammography for the early assessment of breast cancer, 2) enhanced screening and diagnostic workup for pancreatic cancer through multi-omic capabilities to create a multi-modal LBx using peripheral blood and portal vein blood, and 3) a peripheral blood LBx as a substitute to bone marrow aspirate to diagnose myeloma precursor states and detect the transition to multiple myeloma to easily identify candidates for early treatment intervention.