Clinical research with targeted drugs in paediatric oncology

•Drug clonal plasticity and heterogeneity contribute to the development of pharmacological resistances. To minimise treatment failure, research efforts are currently focusing on systematically performing molecular diagnoses at different stages of disease, implementing liquid biopsies as standard practice, including multimodal treatment approaches in clinical trials, introducing targeted drugs earlier in the course of disease, exploiting the use of multitarget kinase inhibitors in certain pathologies, and creating serial tissue sample banking for retrospective analyses.•Future improvements in the way data are managed in Europe depend on the further development of artificial intelligence technologies and data set creation. The European Commission-funded project UNICA4EU seems like a promising platform for such development in paediatric oncology. Another crucial pillar will be the development of an aggregated molecular data set that incorporates data from all current precision medicine trials added to the creation of real-word data sets that integrate information from off-label/compassionate use as well as standard clinical data.•The ITTC-P4 platform has had an enormous impact on the development of preclinical research in Europe to: (i) develop a platform that offers a full set of molecularly characterised preclinical models; (ii) develop a validated method for assessment of the ‘actionability’ of target genes ‘TAR’; and (iii) create a set of guidelines to standardise preclinical data packages and improve translatability of results into the clinic.•The ACCELERATE consortia has created three working groups that tackle essential issues for the creation of efficient drug development plans: (i) The Paediatric Strategic Forums, which are multistakeholder meetings with multitopic discussions on drug development; (ii) The Fit for Filling (FFF) group, which facilitates an industry–academic partnership that ensures the design of academic trials that contribute to marketing authorisation; and (iii) The International Collaborative Group, which coordinates and simultaneously submits investigation plans to US and European Union (EU) regulatory agencies.