PDX Core

项目总结/文摘

PROJECT SUMMARY/ABSTRACT The primary objectives of the Patient Derived Xenograft (PDX) Core will be to establish and characterize PDXs, and to support the research aims of the two integrated research projects of UCaTS, a disparity-relevant studies PDX Development and Trials Center (D-PDTC). The PDX Core will be responsible for the creation and characterization of 120 PDX models in immune-deficient mice (NSG) from tumors of patients with either gastric or lung cancers and diagnosed at any of the six sites: The five NCI designated comprehensive cancer centers (CCC) of the University of California (UC) system (Davis, Los Angeles, San Francisco, Irvine and San Diego) and the University of Texas Southwestern CCC. All of the newly established PDX lines will be from tumors harvested frompatients representing racial/ethnic minorities based on the combined catchment areas we expect to enrich for Latino and Asian American, Native Hawaiians/Pacific Islanders (AANHPI) patients. These PDX models will be used to generate cohorts of specific individual tumor-bearing (PDX) mice for drug efficacy and disparities studies. The PDX Core will consist of the expertise and infrastructure of experienced and capable shared resources at the UCDCCC (The Mouse Biology Shared Resource [MBSR] and the Biorepository Shared Resource [BSR]. Over the last five years, the MBSR and BSR have been involved in establishing, maintaining, characterizing, storing, and distributing numerous PDX models from human patients and PetDX models from veterinary patients in dedicated, highly-contained, and infectious pathogen-free environments. Specifically, during UCaMP, the core implanted 383 distinct tumors which were passaged to successfully establish 101 models in which the majority of models were derived from racially/ethnically communities of color. Further, by engaging qualified and experienced personnel and fully functioning and readily available infrastructure in two preexisting shared resources, the only costs charged to the grant budget are limited solely to PDX modeling services for this project. In this way, the PDX Core will be integral to the successful development of PDX trial strategies for preclinical testing of single agents and drug combinations that can feasibly lead to clinical validation. The PDX Core will also contribute to the PDX Network (PDXNet) by facilitating the deposition of PDX models, tumors, and data into the NCI Patient-Derived Models Repository at the Frederick National Laboratory for Cancer Research so that our models can be shared with the wider research community in addition sharing of the PDXs among UCaTS members. In addition, the PDX Core will also work with the PDXNet to develop and validate SOPs for development and characterization of PDX models for pre-clinical testing.