A video describing PDX mice, minimal information, and why minimal information is needed in the PDX research field.

A figure showing the process of generating and using PDX models.

Abstract Counteracting high failure rates in oncology drug development and improving therapeutic management of cancer patients requires preclinical models that can account for the complexity and heterogeneity of human tumors. Patient-derived cancer xenografts (PDXs) maintain histopathological features and genetic profiles of the original patient tumors and are increasingly recognized as reliable models to predict treatment efficacy and discover sensitivity and resistance biomarkers with immediate clinical relevance.Launched in 2013, the EurOPDX Consortium now gathers 18 academic research institutions throughout Europe and in the US (www.europdx.eu). The goal of the Consortium is to maximize exploitation of PDXs and other patient-derived models for cancer research by: (i) integrating institutional collections into a multicentre repository; (ii) defining common standards to improve the quality and reproducibility of oncology preclinical data; (iii) sharing models within and outside the consortium to perform collaborative precision oncology “xenopatient” trials. Building on its first successes, EurOPDX is now teaming up with other key academic and SME partners in a four-year project to build the “EurOPDX Distributed Infrastructure for Research on patient-derived Xenografts" (EDIReX project, Horizon 2020 grant no. 731105).This new cutting-edge European infrastructure offers access to PDX resources for academic and industrial cancer researchers through 6 state-of-the-art installations or “nodes”. We will present the specific objectives of the project, including our work towards standardization and optimization of biobanking, quality control and data tracking, and the performance of in vivo drug efficacy experiments. Access to the resource, including the distribution of cryopreserved samples from established models, the structured biobanking of user-developed models and the performance of drug efficacy studies, is offered through a grant application system which last deadline is planned mid-June 2020. Selection of the models by users and browsing of PDXs annotation data is made possible thanks to the newly-developed EurOPDX Data Portal (dataportal.europdx.eu), which will display approximately 1,000 models by April 2020 (including 700+ models of colorectal cancer, 80+ gastric and 80+ breast cancer models).We aim to improve preclinical and translational cancer research and promote innovation in oncology by integrating a European PDX repository and facilitating access to this much-needed resource for European and worldwide researchers. Citation Format: Emilie Vinolo, Joaquin Arribas, Andrea Bertotti, Alejandra Bruna, Annette T. Byrne, Robert B. Clarke, Nathalie Conte, Steven de Jong, Didier Decaudin, Zdenka Dudova, Jos Jonkers, Daniela Krasser, Ales Krenek, Luisa Lanfrancone, Eleonora Leucci, Elisabetta Marangoni, Gunhild Mari Maelandsmo, Michaela Th. Mayrhofer, Terrence F. Meehan, Jens Henrik Norum, Hector G. Palmer, Alejandro Piris Gimenez, Leo Price, Sergio Roman-Roman, Francesca Sarno, Violeta Serra, Laura Soucek, Livio Trusolino, Marieke van de Ven, Luca Vezzadini, Alberto Villanueva, Andrea Wutte, Enzo Medico, on behalf of the EurOPDX Research Infrastructure. The EurOPDX Research Infrastructure: Supporting European and worldwide cancer research with patient-derived xenografts [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1685.

Abstract Counteracting high attrition rates in anticancer drug development and providing optimal therapeutic management of cancer patients require preclinical models that properly recapitulate the complexity and diversity of human tumours. Patient-derived cancer xenografts (PDXs), developed by transplanting human tumor fragments into immunodeficient mice, retain the idiosyncratic characteristics of different tumors from different patients. The possibility of population-scale correlations between therapeutic response in PDXs and extensive, multidimensional molecular annotation has enabled the identification of several sensitivity and resistance biomarkers in a number of different tumor types, with immediate clinical relevance. To effectively recapitulate and therapeutically interrogate through patient-derived models the heterogeneity that typifies human cancer, 13 European cancer centres and university hospitals joined forces in 2013 to start EurOPDX, an academic research consortium that now gathers 19 institutions throughout Europe and in the US. EurOPDX includes world-renowned experts at the forefront of research in basic, preclinical, translational and clinical oncology across multiple pathologies, and displays a wide range of expertise in technological platforms. The primary goal of the Consortium is to maximize exploitation of PDXs and other patient-derived cancer models for cancer research by: (i) integrating institutional collections into an organic, multicentre collection of patient-derived models, now reaching 2,000 subcutaneous and orthotopic models for 30+ different pathologies (www.europdx.eu); (ii) defining common operating procedures to improve and standardize molecular and pharmacologic characterization of the models; (iii) sharing models within and outside the consortium to perform collaborative precision oncology “xenopatient” trials, to discover predictive biomarkers, new targets, and new strategies to overcome drug resistance. Towards these objectives, the EC granted 5 million euros under the H2020 programme for a “EurOPDX Distributed Infrastructure for Research on patient-derived Xenografts" - EDIReX EU project n. 731105, starting on February 2018. By teaming up with other key academic, technological and SME partners, our goal with EDIReX is to establish a cutting-edge European infrastructure offering transnational access to PDX resources to academic and industrial cancer researchers, including the distribution of cryopreserved samples to third parties, the structured biobanking of user-developed models, and the performance of drug efficacy studies. We will provide an overview of the current achievements of the Consortium and the objectives of the EDIReX project. Citation Format: Enzo Medico, Mohamed Bentires-Alj, Andrew V. Biankin, Alejandra Bruna, Annette T. Byrne, Carlos Caldas, Robert B. Clarke, Georges Coukos, Olivier Elemento, Manuel Hidalgo, Giorgio Inghirami, Steven de Jong, Jos Jonkers, Ales Krenek, Eleonora Leucci, Gunhild Mari Maelandsmo, Michaela Th. Mayrhofer, Terrence F. Meehan, Simone P. Niclou, Pier Giuseppe Pelicci, Alejandro Piris-Gimenez, Leo Price, Sergio Roman-Roman, Livio Trusolino, Luca Vezzadini, Alberto Villanueva, Emilie Vinolo, on behalf of the EurOPDX Consortium. The EurOPDX EDIReX project: Towards a European research infrastructure on patient-derived cancer models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 985.

Abstract Patient-derived tumor xenograft (PDX) mouse models have emerged as an important oncology research platform to study tumor evolution, mechanisms of drug response and resistance, and tailoring chemotherapeutic approaches for individual patients. The lack of robust standards for reporting on PDX models has hampered the ability of researchers to find relevant PDX models and associated data. Here we present the PDX models minimal information standard (PDX-MI) for reporting on the generation, quality assurance, and use of PDX models. PDX-MI defines the minimal information for describing the clinical attributes of a patient's tumor, the processes of implantation and passaging of tumors in a host mouse strain, quality assurance methods, and the use of PDX models in cancer research. Adherence to PDX-MI standards will facilitate accurate search results for oncology models and their associated data across distributed repository databases and promote reproducibility in research studies using these models. Cancer Res; 77(21); e62–66. ©2017 AACR.

Nature Reviews Cancer 17, 254–268 (2017) In the online html version of this article, Joan Seoane's affiliations were not correct. He is also a member of the EurOPDX Consortium and is at the Vall d'Hebron Institute of Oncology, 08035 Barcelona, the Universitat Autònoma de Barcelona, 08193 Bellaterra,and the Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Spain.

e22056 Background: Triple negative breast cancer (TNBC) is associated with aggressive histological features, high relapse rates, and poor overall survival. To improve the management of TNBC patients, there is an unmet need to develop noninvasive biomarkers to monitor treatment efficacy. TP53 mutations are clinically relevant in TNBC since they present in 60-88% of TNBC cases. Thus, circulating cell free tumor DNA (ctDNA) identified by TP53 mutations could serve as a “liquid biopsy” for TNBC tumors. In this study we measured the mutant TP53 fraction in ctDNA of metastatic TNBC patients by next generation sequencing (NGS) and compared our results to Circulating Tumor Cell (CTC) numbers. Methods: 36 women with metastatic TNBC and receiving a new line of systemic therapy were enrolled in this study. DNAs from 36 solid tumors and 56 plasma samples were extracted and amplified using a panel of target specific primers covering all the exons of TP53 and sequenced as described by the TAMSeq protocol. This method uses a microfluidic chip, the Access Array by Fluidigm, to perform PCR enrichment and Illumina bi-directional sequencing. CTC were enumerated by CellSearch technique. Results: Performance status, elevated LDH and CTC≥5/7.5 ml, were significant prognostic factors for overall survival. TP53mutations were identified in 27 (87%) of 31 solid tumor samples. Five FFPE tumor samples were not analyzable due to the fixation process. The same mutation was identified in the ctDNA of 22 (81%) matched plasma samples and the mutant allele contributed to 2-70% total circulating DNA. A decrease of mutant DNA percentage was observed in a second plasma sample during treatment in 8 (66%) of 12 patients. CTCs were ≥5/7.5 ml at baseline in the blood of 16 (50%) of the 32 patients analyzed and their numbers were not correlated with ctDNA concentration levels. Conclusions: ctDNA TP53 analysis by NGS represents a promising approach to assess treatment efficacy in TNBC. In addition, this method could be used when the primary tumor is not available and undetermined mutations need to be identified from a patient’s plasma DNA.

Abstract The EurOPDX Consortium is an initiative of translational and clinical researchers from 14 cancer centers and universities across 9 European countries, with the common goal of creating a network of clinically relevant models of human cancer, and in particular patient-derived xenograft (PDX) models. PDX models, which are generated by transplantation into an immunodeficient mouse of a patient's tumor obtained fresh from surgery, are broadly implemented for all cancer pathologies by translational laboratories (Tentler et al., 2012). Grafted tumors have been shown to maintain high similarities with the original patient tumor. Hence, preclinical trials in large panels of models recapitulating the intertumor heterogeneity of human cancer have been shown to reproduce data obtained in clinical trials (Bertotti et al., 2011; Julien et al., 2012). The primary goal of the EurOPDX Consortium is to share PDX models and perform collaborative multicenter and multipathology "xeno patient" trials within molecularly defined tumor subsets, resulting in hypothesis-driven personalized medicine strategies for cancer patients. Altogether, the Consortium displays a panel of more than 1,500 PDX subcutaneous and orthotopic models in more than 30 pathologies, including for instance 640 models obtained from primary tumors or metastases of colorectal cancer, 200 models of pancreatic cancer, and over 120 models of breast cancer. The characterization of models will be harmonized and will include deep molecular profiling and pharmacogenomic data corresponding to current anticancer therapies. Through implementation of a shared database and the emergence of a common biobank of patient-derived viable cancer specimens, the Consortium will use characterization data to identify novel strategies for pinpointing new targets and overcoming drug resistance, and will validate therapeutic hits in collaborative multicentric preclinical trials. Best practices for the performance of such trials in mice will be implemented, with the goal of advancing their predictivity for success in the clinic. The Consortium will also generate new PDX models and integrate complementary models such as ex vivo 2D and 3D assays to achieve research goals. Implementing PDX models in the discovery of predictive biomarkers for targeted therapies will be a key objective. This initiative will create a pipeline that will greatly accelerate and advance the development of novel therapeutic strategies and their validation for cancer treatment, through more predictive preclinical or "co-clinical" data. Through this collaborative effort that is to our knowledge, unique in Europe, and the participation of pharmaceutical companies and SMEs involved in drug development, we aim to reduce the duplication of efforts in oncology drug development, ultimately improving the quality of life and overall survival of cancer patients. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):A8. Citation Format: Emilie Vinolo, Elisabetta Marangoni, Violeta Serra, Frederic Amant, Andrea Bertotti, Andrew V. Biankin, Anne-Lise Børresen-Dale, Alejandra Bruna, Eva Budinská, Annette Byrne, Carlos Caldas, David Chang, Robert Clarke, Els Hermans, Manuel Hidalgo, Steven de Jong, Jos Jonkers, Pedro López, Gunhild Mari Mælandsmo, Vlad Popovici, Sergio Roman-Roman, Joan Seoane, Livio Trusolino, Alberto Villanueva, on behalf of the EurOPDX Consortium. The EurOPDX consortium: Sharing patient tumor-derived xenografts for collaborative multicentric preclinical trials. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr A8.