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Summary  Cancer remains the leading cause of death from disease among children beyond the age of one. Survival of pediatric patients with cancer has dramatically improved over the last decades but some tumors remain almost intractable and relapse is still associated with an infaust prognosis. Despite the heterogeneity of pediatric malignancies, most treatments include the same set of generic therapies.  Optimizing delivery of conventional therapeutics has been the driving force behind continuous improvements but further escalation of conventional therapy is unlikely to improve outcomes. The limited success of targeted drugs in pediatric cancer patients, originally developed for cancers in adults, can be connected to the different etiology of tumors in children versus adults. In addition, many pediatric cancers lack reliable biomarkers, cannot be studied in large cohorts and only few available therapies target abberations specific for certain pediatric cancers.  These observations have led to the establishment of pediatric precision-medicine programs. The major goal of these programs is to identify patient-tailored molecular treatment plans that will eventually improve quality of life and survival. Despite the initial euphemism, the impact of actionable matched treatments and the most adequate value-based genomics strategies are not yet well established. A non-competitive collaborative model based on pediatric cancer priorities and strong collaboration between academia, pharmaceutical companies and regulators is needed. In the near future, clinical trials need to focus on biologically defined patient subsets, in an even smaller patient population. A major collaborative effort between all associated groups will be necessary to ensure success of pediatric precision cancer medicine.

Therapy concepts in the context of precision medicine for pediatric malignancies—children are not adults