BACKGROUND AND OBJECTIVES
- Patients-derived xenograft (PDX) mouse models are an important oncology research platform to study tumor evolution, drug response and personalised medicine approaches.
- Because of the distributed and heterogeneous nature of PDX repositories, finding relevant models of interest to investigators is a challenge.
- The global success of PDX models will depend on their collective distribution and usage worldwide by academic and private sectors.
- To facilitate PDX models discovery, EMBL-EBI and The Jackson Laboratory are co-developing PDX Finder – a comprehensive open global catalogue of PDX models and their associated data across resources. In support of this initiative, we coordinated the community initiative to develop the PDX models Minimal Information standard (PDX-MI) that defines the minimal information necessary for describing key elements of a PDX model including the clinical attributes of a patient’s tumor, methods of implantation, host strain, and quality assurance methods used for model validation.
- PDX-MI serves as the basis for PDX Finder’s comprehensive search and attribute filtering options (e.g., tumor histology, molecular variant, drug response).
- Within PDX Finder, model attributes are harmonized and integrated into a cohesive ontological data model that supports consistent searching across the originating resources.
- Integrated views will be provided for histopathological image data, molecular classification of tumors, host mouse strain metadata, tumor genomic data, and metrics on tumor response to chemotherapeutics.
- From PDX Finder, direct links to these resources are provided to allow users to contact the relevant institution for model acquisition and further collaboration.
- More details about the PDX data submission, integration and distribution can be found in data flow.
This work is supported by the National Institutes of Health U24 CA204781 01 (ended 31.08.2020), U24 CA253539 01 and the National Cancer Institute MTB R01 R01CA089713.
PDX mouse model creation
Schematic of the process for PDX model creation, expansion, and drug dosing studies. A PDX model consists of an immunocompromised mouse into which human tumor material has been implanted. Once the implanted tumor reaches a target volume at the initial passage (P0), the tumor is excised, fractionated, and transplanted into the next cohort of mice to establish the next passage. P0 and P1 tumors are subjected to various quality control assays to ensure that the passaged tumors faithfully reflect the critical biological and genomic properties of the patient tumor. Cohorts of tumor-bearing mice are used in experimental studies. Dosing studies are typically performed on low passage tumors (P1-P4).