Project Summary/Abstract: The overall goal of the University of Pennsylvania PDX Development and Therapeutics Center (UP-PDTC) is to (i) exploit the translational potential of PDX models for evaluating the response of various treatments in models with specific molecular characteristics and to (ii) work with PDXNet to enhance and extend use of PDX models to the research community with the goal to guide development of human Phase 1/2 clinical trials for human malignancies. As PDX models more faithfully reproduce human cancer than cell lines, they can contribute to the ultimate clinical implementation of cancer precision medicine. The UP-PDTC is uniquely poised to contribute to such research due to the long history of PDX research at UPENN. The UP-PDTC will comprise 4 Cores and 2 projects. The four Cores are: Administrative, PDX, Pilot Projects and Trans-Network, and a Bioinformatics Core. The Administrative Core will coordinate all UP-PDTC activities. The PDX Core builds on 15 years of experience within the Stem Cell and Xenograft Core facility of UPENN. The PDX Core currently provides over 900 mice per month to investigators at UPENN using PDX modeling for malignant and non-malignant disease. The animal facility of the PDX Core is a dedicated 6 room suite controlled by highly skilled PDX Core personnel with comprehensive infection control measures. Using these measures, the PDX Core has not had a significant infection in the colony in seven years. The Pilot Projects Core will take advantage of a growing group of collaborators to build tissue banks for hepatocellular carcinoma (HCC), clear cell renal cell carcinoma (ccRCC), breast cancer, glioblastoma, and myeloma. A major goal of the UP-PDTC is to develop and characterize new models across common and rare cancer types that can be linked with the originating patient clinical response profile and shared with PDXNet. The Bioinformatics Core takes advantage of the extensive Bioinformatics infrastructure at UPENN and will work with the Projects to more rigorously describe PDX modeling for acute myeloid leukemia (AML) and ovarian cancer. There are two projects. Project One is directed by Dr. Martin Carroll and will focus on acute myeloid leukemia. Project 1 takes advantage of one of the largest tissue banks of viable, fully annotated AML samples in the world. This tissue bank currently has over 3300 collections from over 1700 patients collected over 20 years including over 40 PDX primograft models currently available of over 100 that have been described. Dr. Carroll, working with members of the PDX Core, has a long history of developing and using the AML PDX model to define AML biology and responses to therapy. Project 2 is directed by Dr. Fiona Simpkins and takes advantage of the Ovarian Cancer Research Center Tumor BioTrust Collection. This collection is fifteen years old, also fully annotated and includes 140 well characterized PDX models. Drs. Carroll and Simpkins, have extensive experience in xenot...