The Landscape of Pediatric Precision Oncology: Program Design, Actionable Alterations, and Clinical Trial Development

SIMPLE SUMMARY: Precision medicine is a revolutionary new way to deliver cancer treatment by targeting specific genetic changes of the cancer of the individual child with the goal of improving cure rates and reducing toxicity. In this review, we illustrate the evolution of cancer treatment in this groundbreaking new era. We compare characteristics and early results of precision medicine programs in pediatric oncology as well as novel clinical trial initiatives translating these findings into potential clinical benefit for all children and adolescents with cancer. ABSTRACT: Over the last years, various precision medicine programs have been developed for pediatric patients with high-risk, relapsed, or refractory malignancies, selecting patients for targeted treatment through comprehensive molecular profiling. In this review, we describe characteristics of these initiatives, demonstrating the feasibility and potential of molecular-driven precision medicine. Actionable events are identified in a significant subset of patients, although comparing results is complicated due to the lack of a standardized definition of actionable alterations and the different molecular profiling strategies used. The first biomarker-driven trials for childhood cancer have been initiated, but until now the effect of precision medicine on clinical outcome has only been reported for a small number of patients, demonstrating clinical benefit in some. Future perspectives include the incorporation of novel approaches such as liquid biopsies and immune monitoring as well as innovative collaborative trial design including combination strategies, and the development of agents specifically targeting aberrations in childhood malignancies.