Patient-Derived Xenograft Shared Resource

PROJECT SUMMARY/ABSTRACT - PRE-CLINICAL PDX MODELS SHARED RESOURCE (PDXSR) The Pre-Clinical PDX Models Shared Resource (PDXSR) of the Dan L Duncan Comprehensive Cancer Center (DLDCCC) meets the needs of DLDCCC investigators wishing to use robust, state-of-the-art in vivo cancer models that require specialized techniques and a high degree of experimental ingenuity. These models include patient-derived tumor xenografts (PDX) grown in either immunocompromised mice or rats or in alternative platforms, including patient-derived tumor organoids, xenograft-derived organoids (PDxO), or 3D tumor growth on the chicken egg chorioallantoic membrane (CAM). All models provide users with renewable resources annotated with a comprehensive clinical history and fully characterized with multi-omics data that are accessible/mineable to assist with experimental design. Both PDxO and CAM 3D models can be adapted for screening investigational therapeutic compounds rapidly and efficiently, and these models can be genetically engineered to enhance their utility as experimental models. All models are rigorously validated to “credential” that they accurately reflect the biology of the disease or process under study. Because patient-derived tissues used to generate these models harbor considerable clinical and omic information, the PDXSR provides computational infrastructure to abstract, store, organize, retrieve, and display such information so investigators can rationally select which model(s) to use and interpret their results. PDX models established from patients with bladder, breast, gynecological, head and neck, lung, or pancreas cancer, as well as glioblastoma, leukemia, or sarcoma, have whole-exome sequencing WES, RNAseq, and baseline proteomic profiling data available. When possible, matching patient germline WES data are also obtained and made available. In collaboration with other omics SRs (PSR, MSR, GSTESC SR), PDXSR participates in a workflow pipeline for multi-omics analysis of PDX frozen tumors and matching human biopsies when available. Once omics data are collected and processed, they are made available on our newly enhanced PDX Portal “Insights” web-based data display and analysis tool. This website portal integrates patient- and PDX-related data to enable selection of models for pre-clinical research without additional input from bioinformaticians. A major support service is training SR users on animal handling, surgical procedures and use of imaging instrumentation required to establish and perform experiments with PDX models. Future initiatives include: 1) determining the utility of humanized mouse models possessing human immune system components in conjunction with PDX models to evaluate immunotherapies; 2) developing unique methods for PDX genetic modification; and 3) increasing experimental throughput using PDX-derived material for genetic and drug screening. The PDXSR will coordinate these activities for DLDCCC investigators to enhance in vivo model access and utilization in a cost-effective manner.