Under the coordination of the University of Turin in Italy, members of the EurOPDX Consortium and additional key European academic and SME partners recently secured 5 million € from the European Union’s Horizon 2020 research and innovation programme to build an infrastructure for access to patient-derived cancer xenograft (PDX) models and related data, for academic and industrial, preclinical and translational cancer research.
The EurOPDX Consortium
Counteracting high failure rates in the development of new treatment strategies in oncology and improving therapeutic management of cancer patients requires preclinical models that can account for the complexity and heterogeneity of human tumours. PDX models, which maintain histopathological features and genetic profiles of the original patient tumours, are increasingly recognised as reliable research models to predict treatment efficacy and discover biomarkers.
Numerous small- to mid-scale collections of PDX models for various cancer types have been established by academic laboratories across Europe, which are currently poorly visible and only exchanged on a discrete collaborative basis. This presents a bottle-neck to the use of these valuable resources and results in unnecessary redundancy of PDX models, which are time-consuming and expensive to establish and characterise. In addition, each research group develops its own methodologies, with few comparative studies being conducted. The EurOPDX Consortium was established 5 years ago as an initiative toward the integration of a number of PDX collections, and has been leading the way in raising standards and promoting scientific collaboration in PDX research in Europe (www.europdx.eu).
Towards the EurOPDX Research Infrastructure
This newly funded project named EDIReX (“EurOPDX Distributed Infrastructure for Research on patient-derived cancer Xenografts”), involves 19 partners from 13 European countries and aims to further the reach of the EurOPDX Consortium by offering free-of-charge access to a large PDX resource for academic and industry researchers in Europe and Worldwide. Such a resource is currently lacking in Europe and is much-needed to increase the predictability of preclinical data through the use of more reliable cancer models.
Under the leadership of two major IT partners (Masaryk University and EMBL-EBI), a public repository will be developed integrating a shared collection of over 1500 established PDX models with their clinical, molecular and pharmacological annotation, to facilitate data sharing and selection of models of interest by users. Data will be accessible in particular through the recently launched PDX Finder, a catalogue of PDXs co-developed by the EMBL-EBI and the Jackson Laboratory (www.pdxfinder.org). The EurOPDX repository will also include an innovative tool for improvement of the user experience with 3D visualisation of data, developed by the Italian SME Kairos3D. Access to models will be offered through six state-of-the-art partner facilities or “nodes” in the following institutions: University of Turin (Italy), Katholieke Universiteit Leuven (Belgium), Netherlands Cancer Institute (The Netherlands), University of Cambridge (UK), Institut Curie (France), and Vall d’Hebron Institute of Oncology (Spain). The provision of access will require the “nodes” and the other PDX providers to work toward standardisation and optimisation of biobanking, quality control and data tracking, and the performance of in vivo drug efficacy experiments. We aim to further support the deployment of global and sustainable standards thanks to the pre-existing links between project partners and other related international initiatives.
In addition, the European infrastructure BBMRI-ERIC will bring its expertise in quality management and ethics, and will provide valuable strategic input for the sustainability of the infrastructure.
“Our work on the definition of standards in the field will not only be crucial for the establishment of the infrastructure distributed across 6 nodes, but will also improve the quality and reproducibility of oncology preclinical data on a global scale”, further emphasizes Prof. Enzo Medico, Coordinator of EDIReX (University of Turin, Candiolo Cancer Center IRCCS, Italy). “In addition, we will perform a large comparative study of the standard subcutaneous PDX models with more innovative models (including ex vivo tests performed by the Dutch Contract Research Organisation, OcellO), combined with advanced preclinical imaging, to prepare for future services of the infrastructure and improve its contribution to innovation in cancer research.”
The contribution of the researchers Alberto Villanueva (IDIBELL-ICO) and Purificación Muñoz (IDIBELL) to the project focuses on the generation and use of orthotopic models of colon cancer. In fact, Villanueva is a member of the Board of Directors of EurOPDX, so he has been closely involved in the development of this new research structure.
Modalities of access & Announcement of the first call for proposals in October 2018
Access to the PDX resource will be offered through a grant application system which will open in October 2018. The grant will offer successful applicants the opportunity to receive tissue samples from PDX models listed in the newly developed EurOPDX repository, or deposit one of their own models at one of the six “nodes”, for inclusion in the public repository, allowing access to their resource by the wider scientific community. As from the 2nd call (planned in 2019), the nodes will also perform in vivo drug efficacy studies for selected users, and in particular oncology biotechnology companies.
The EDIReX webpage, launched this week (www.europdx.eu/europdx-research-infrastructure), provides further details of the objectives of the project and centralises information on the established standards, the opportunities for access and the modalities of applications.