Abstract
Patient Derived Xenografts (PDX) are a powerful technology with the potential to unlock key mechanisms of disease for a variety of difficult to treat cancers and cancers with no applicable laboratory models. These models have a wealth of potential applications in tumor genetics, biomarker discovery, progression of metastasis, fate of circulating tumor cells, and in drug development of novel therapies for advanced and drug-resistant tumors. While several individual laboratories can excel at establishing such models, there are challenges, both procedural and technical, which present serious obstacles for established investigators as well as new investigators without prior experience with PDX models. Therefore, for some Institutions it is preferable to designate a centralized “PDX Core” to streamline the workflow that is required for the success of such program.
Here we describe and analyze the key components of a successful Academic PDX program. The PDX coordination branch carries out administrative duties to guarantee that the multiple components involved in generating PDXs are seamlessly integrated. In particular, it deals with logistical tasks including regulatory requirements (IRB, patient consent forms, IACUC), and sample accrual (patient selection, coordination with surgery schedules, specimen collection). In addition, it takes care of database maintenance and interface with clinical applications. The PDX laboratory branch meanwhile devises and implements standard operating procedures for sample processing, storage and implantation, and model maintenance, PDX characterization and distribution, and takes care of training of specialized personnel.
The establishment of such centralized PDX core at MSKCC resulted in a tenfold increase in the Institution's ability to generate PDX models within a year of inception of the program. In particular, for ongoing projects, we observed an increase not just in sample accrual but also in tumor take rate. In addition, the number of different tumor types implanted expanded substantially, from six to over twenty.
PDXs have the potential to be invaluable tools in understanding cancer and developing novel treatments. In our experience, the establishment of a centralized PDX core is both the most cost effective and efficient way for academic investigators to generate and gain access to novel, well characterized, and clinically annotated PDX models.
Citation Format: Marissa Mattar, Rajesh K. Uthamanthil, Elisa de Stanchina. Establishment and maintenance of a PDX Core Facility. [abstract]. In: Proceedings of the AACR Special Conference: Patient-Derived Cancer Models: Present and Future Applications from Basic Science to the Clinic; Feb 11-14, 2016; New Orleans, LA. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(16_Suppl):Abstract nr B30.