United for Health Equity - Living PDX Program (U4HELPP)

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PROJECT SUMMARY/ABSTRACT – OVERALL The United for Health Equity-Living PDX Program (U4HELPP) seeks to develop >500 new patient-derived xenograft (PDX) models of cancers originated from the breast, pancreas, colon, liver, lung, and other advanced peritoneal cancers. These PDXs will be made from >60% of patients from underrepresented populations which our safety-net clinical system serves. To develop such a large number and diverse set of PDXs, we have enlisted the support of a set of surgeons that specialize in each cancer type. Once extracted, the tumors are immediately provided to the U4HELPP PDX Core which functions to propagate, distribute, and cryopreserve them. Successfully generated PDXs will be subjected to genomic characterization and quantitative ancestral profiling by the U4HELPP Bioinformatics Core so that we can better understand how ancestry contributes to genetics and responses to targeted therapeutics. The PDXs will be provided to two Research Projects, that will focus on either pancreatic cancer or breast cancer. The Pancreatic Cancer project will generate large-scale proteomics insights from over 200 PDXs to refine subtypes of the disease and identify more effective therapeutics from Black and White patients. The Breast Cancer project will utilize 20 PDXs that are Basal-like breast cancers, characterize their metastatic profiles, define proteogenomic pathways that mediate metastatic growth, and target metastases with synergistic investigational new drug combinations. The information from these PDXs and Projects will be shared with the U4HELPP Pilot Projects and Trans-Network Activities Core which will award Pilot Project grants to utilize the PDXs generated by us and our partnering PDXNet institutions. All of the PDXs and insights gained will be shared with the NCI with the goal of reducing cancer disparities. Through this team effort we are confident that we will be able to develop these unique resources and generate significant preliminary data that will support investigator initiated clinical trials at the Massey Cancer Center.