Periodic Reporting for period 3 - EDIReX (EurOPDX Distributed Infrastructure for Research on patient-derived cancer Xenografts) Période du rapport: 2021-02-01 au 2022-07-31 Résumé du contexte et des objectifs généraux du projet Counteracting high failure rates in oncology drug development and providing optimal therapeutic management of cancer patients require research models that properly recapitulate the complexity and diversity of human tumours. Patient-derived tumour xenografts (PDXs), established by transplanting tumour fragments into immunodeficient mice, are being widely embraced by the scientific community as reliable preclinical tools for efficient drug development and tumour biology studies.The EurOPDX Consortium, established in 2013 by researchers developing and using PDX models, has been teaming up with other key academic and industry partners to build the EurOPDX Research Infrastructure (RI, www.europdx.eu). Our overall goal was to establish a cutting-edge distributed European RI offering access to PDX models and associated data and services for academic and industry cancer researchers, notably through free-of-charge trans-national access.We have been integrating and curating a collection of over 1,000 PDXs established and validated by EurOPDX members in a new repository, the EurOPDX Data Portal (https://dataportal.europdx.eu). The Data Portal allows efficient and user-friendly query and visualisation of clinical, molecular and pharmacological annotation of the models. Access by the 6 nodes of the RI includes the distribution of cryopreserved samples to academic laboratories, the structured biobanking of user-developed models, and the performance of drug efficacy studies in particular for oncology SMEs. To ensure interoperability in services, we have established and are applying standard procedures for PDX quality control, health monitoring, long-term storage and therapeutic mouse trials. Access has been available through a grant programme, with 3 calls open in the frame of this 4-year project.We aim to ensure the sustainability of this new RI. In this objective, we have also been preparing for the future provision of innovative services such as orthotopic and humanised PDX models, the use of multimodal imaging techniques, as well as in vitro PDX-derived cells. While there are still many challenges ahead, we successfully delivered on the activities above and provided access to PDX services for several users under the project. Overall, the EurOPDX RI activities and services will contribute to more reliable and predictable preclinical studies and therefore more efficient development of new therapeutic strategies for cancer patients. Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent We have delivered on the set-up of the new EurOPDX Research Infrastructure (RI) providing high quality preclinical cancer research models and results for EU and global cancer researchers:- Our repository EurOPDX Data Portal (https://dataportal.europdx.eu) now includes over 1,000 curated PDX models from 9 different European research centres and 10 cancer types. It is powered by the PDX Finder, a global repository developed by our project partner EMBL-EBI together with The Jackson Laboratory. The Data Portal currently links molecular data to a EurOPDX instance of the cBioPortal, an open-source tool widely used by the cancer research community to explore cancer genomics data. In addition, an innovative tool for 3D visualization was developed with the SME Kairos3D for future improvement of user data exploration experience;- To ensure interoperability between the 6 RI nodes and increase the quality of models and samples, we have established standard operating procedures (SOPs) for the biobanking and quality control of PDXs. Our health monitoring procedure is already available on our website (www.europdx.eu/standards) whereas other standards will be published beyond the project. The nodes are also all equipped with the same laboratory information management system used to track the biobanking and intervention studies data, allowing the performance of multicenter studies;- The established standards have been applied in the delivery of access to RI users, but also in an unprecedented cross-validation study performed by the 6 nodes and additional centres to compare results using the same PDXs and same drugs across centres and patient-derived platforms (subcutaneous, orthotopic, humanized, in vitro). The results of this study will showcase the interoperability of the RI installations and highlight important aspects of PDX research and in general cancer research using patient-derived models. A publication is under preparation;- Thanks to our procedures established to manage the trans-national access grant programme and selection of successful applicants (see https://www.europdx.eu/europdxri-ta) we have run 3 different calls for proposals with 4 deadlines. This led to the selection of 18 excellent user projects, for which users were able to select models in the Data Portal. Several projects have been delivered and others are being completed;- We have worked on the sustainability through the hiring of a RI Manager trained to the specific management of European RIs. We are already participating to the starting canSERV project with major biomedical RIs to support the Cancer Mission through the provision of cutting-edge cancer research services (https://www.canserv.eu);- Finally, the project and our activities have been widely disseminated through our new website (www.europdx.eu) Twitter account (@EurOPDX), and presentation to conferences, and we organized two EurOPDX Workshops in 2018 and 2022 to discuss important aspects of PDX research with the community and train early-stage researchers. Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent) Until about 5 years ago, the practice of exchange of PDX models data was only following ad-hoc informal procedures, quite frequently sending Excel files only, with no thorough unification of format and semantics, and no centralised and harmonised comprehensive information on the establishment and characterisation of each particular PDX model. With the increase in PDX models and providers this process was not sustainable anymore. Thanks to our IT partners and the development of the PDX Finder and the EurOPDX Data Portal, we are now providing cancer researchers with a gateway to distributed collections of established and validated models. This will greatly improve PDX collaborative research and optimise the use of this previous resource.In addition, standards in the field have been lacking. The establishment of our SOPs and their dissemination will have a great impact on the reliability and reproducibility of preclinical data using PDXs. Of note, our results in collaboration with the US PDX network PDXNet published in Nature Genetics early 2021 (Woo, Giordano et al.) bolster the value of PDXs as representative models for preclinical cancer research.The repository and the standards were key to the set-up of the new EurOPDX Research Infrastructure providing access to PDXs, filling a gap in the services provided so far by established biomedical European Research Infrastructures.We have also tested in the project the provision of more innovative services, toward more predictive preclinical data and further minimising the use of animals through the use of PDX-derived in vitro models.In summary, the EurOPDX Research Infrastructure succeeded in the first steps to become a reference for preclinical testing of new therapeutic interventions in Europe, thereby improving and accelerating preclinical oncology research in Europe and worldwide to the ultimate benefit of patients and society. Image of the 3rd workshop held in person in the Netherlands in 2022 Snapshot of the EurOPDX Data Portal, the public repository for EurOPDX patient-derived xenografts
