PDX Core

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PDX CORE SUMMARY The Patient Derived Xenograft (PDX) Core is the epicenter of the Washington University PDX Development and Trial Center (WU-PDTC). It will be responsible for the development, organization, characterization, storage, and dissemination of high quality pathogen free PDX models for research projects investigating anticancer agents, within and outside of WU-PDTC. Leveraging prior success and streamlined and efficient infrastructure, the PDX Core will continue PDX development with a focus on creation of high-value specimens from biologically prioritized specimens (e.g. treatment resistant cases). The Human and Mouse Linked Evaluation of Tumors (HAMLET) PDX Core at the Institute of Clinical and Translational Study (ICTS) and the Solid Tumor Tissue Bank and Registry (STTBR) led by Drs. Li and Fields, respectively, have a proven record of success in generating PDX models from a wide variety of cancers and in utilizing these models for drug testing. These synergistic programs have generated >1,000 models from >15 solid tumors, including large cohorts of recalcitrant cases (e.g. treatment resistant pancrcreatic and triple-negative breast cancer) and genomically similar (e.g. HER-2 amplified) solid tumors that have led to multiple clinical trials in the ETCTN. These existing models will become part of the renewal WU-PDTC, where ~400 new PDX models will be developed and added to this collection. The new PDX models will further enhance our capability to support ongoing projects and open new opportunities for research in clinically prioritized cancer themes. Taking advantage of the strong proteogenomic capability within the proposed WU-PDTC and WUSM, we will expand the characterization of these PDX models to include cutting- edge genomics, transcriptomics, proteomics, and metabolomics. This will provide investigators with a more comprehensive picture of the mutational profiles, the molecular signatures, clonal structures, and heterogeneities of the models to help with cancer sub-typing and target selection. Besides research projects at WU-PDTC, PDX models in the PDX Core collection will also be shared with other PDTCs and made broadly available to authorized non-network investigators. Existing infrastructure copuled with the large clinical oncology program at WU and exceptionally strong institutional support, including matching funds, will ensure that the goals of the WU- PDTC PDX Core goals are achievable.