Pre-clinical drug development for paediatric cancers is very complex, resource intensive and requiring multi-disciplinary expertise and innovative approaches. The VAGABOND ITN, consisting of 12 academic and 6 non-academic partners from 8 European countries, aims to create a multidisciplinary and multi-sectoral program to validate new therapeutic interventions in paediatric cancer. This network will be sustainable embedded in the ITCC (Innovative Treatments for Children with Cancer) Consortium. The VAGABOND ITN will focus on 15 cutting-edge research projects studying molecular, epigenetic and immunological targets. All projects will (partly) include target identification, in vitro and in vivo validation, compound testing and preparation for clinical implementation. This consortium will highly stimulate international education and multi-disciplinary exchange of expertise in the different steps of pre-clinical drug development. This setting provides an opportunity for a unique European training network in which early stage researchers are equipped with a broad knowledge in pre-clinical drug development. Through this network students will gain access to other leading academic research groups, specialized multi-sectoral companies and the most innovative techniques and insights in the complexity of translational medicine to prepare them for future challenges in their career pathway. In this collaboration we will increase the commune expertise on tumour types and technical expertise for target validation. This will improve the implementation of interventions across paediatric cancer and strongly reduce the timeline from bench to the bedside.

PRIMAGE proposes a cloud-based platform to support decision making in the clinical management of malignant solid tumours, offering predictive tools to assist diagnosis, prognosis, therapies choice and treatment follow up, based on the use of novel imaging biomarkers, in-silico tumour growth simulation, advanced visualisation of predictions with weighted confidence scores and machine-learning based translation of this knowledge into predictors for the most relevant, disease-specific, Clinical End Points. PRIMAGE implements a hybrid cloud model, comprising the of use of open public cloud (based on EOSC services) and private clouds, enabling use by the scientific community (facilitating reuse of de-identified clinical curated data in Open Science) and also suitable for future commercial exploitation. The proposed data infrastructures, imaging biomarkers and models for in-silico medicine research will be validated in the application context of two paediatric cancers, Neuroblastoma (NB, the most frequent solid cancer of early childhood) and the Diffuse Intrinsic Pontine Glioma (DIPG, the leading cause of brain tumour-related death in children). These two paediatric cancers are relevant validation cases given their representativeness of cancer disease, and their high societal impact, as they affect the most vulnerable and loved family members. The European Society for Paediatric Oncology, two Imaging Biobanks and three of the most prominent European Paediatric oncology units are partners in this project, making retrospective clinical data (imaging, clinical, molecular and genetics) registries accessible to PRIMAGE, for training of machine learning algorithms and testing of the in-silico tools´ performance. Solutions to streamline and secure the data pseudonymisation, extraction, structuring, quality control and storage processes, will be implemented and validated also for use on prospective data, contributing European shared data infrastructures.

Cancer remains the leading cause of disease-related death in children. For the ~25% of children who experience relapses of their malignant solid tumors, usually after very intensive first-line therapy, curative treatment options are scarce. Preclinical drug testing to identify promising treatment options that match the molecular make-up of the tumor is hampered by the facts that i) molecular genetic data on pediatric solid tumors from relapsed patients and thus our understanding of tumor evolution and therapy resistance are very limited to date and ii) for many of the high-risk entities no appropriate and molecularly well characterized patient-derived models and/or genetic mouse models are currently available. Thus, quality-assured upfront preclinical testing of novel molecularly targeted compounds in a (saturated) repertoire of well-characterized models will establish the basis to increase therapeutic successes of these drugs in children with solid malignancies. Since these tumors are overall genetically much less complex than their adult counterparts, it is anticipated that it will be easier to identify powerful predictive biomarkers to allow for accurate matching of targets and drugs. To address this high, as yet unmet clinical need, we have formed the ITCC-P4 consortium consisting of academic and commercial partners from 8 European countries and covering the full spectrum of qualifications needed for quality-assured preclinical drug development including expertise in patient derived models, histopathology, in vivo pharmacology, bioinformatics and data management, centralized testing capabilities, medical expertise regarding the entities in question, regulatory knowledge, and project management of large consortia. With this consortium in a public-private partnership with the participating pharma companies we strongly believe to be ideally positioned to greatly expedite the development of more precise and efficacious drugs for children with malignant solid tumors