Building bridges: precision medicine in pediatric oncology

Abstract

Childhood cancer is the leading cause of death in children and young adults in developed countries. To improve outcomes and minimize side effects, the field of “precision medicine” is being explored, aiming to select treatments based on unique characteristics of cancer cells. Large-scale studies analyzing DNA and RNA traits of pediatric cancer have shown major differences between cancers in children and adults. Over 50% of tumors have shown alterations that might make them sensitive to specific drugs. However, efficacy of targeted treatments remains challenging to predict. Therefore, novel functional methods including drug sensitivity testing on tumor derived cells (“organoids”) are investigated to complement aforementioned approaches. In this thesis, we summarize advancements in precision medicine in pediatric oncology. We present results of the Dutch precision-oncology program "iTHER", which analyzed over 300 samples of pediatric tumors and found alterations to support treatment with specific medicines. While the study produced promising results, translation to clinical practice has been limited by the low number of patients treated accordingly. Subgroups of patients with high-priority targets in a large international cohort are shown to benefit from targeted treatment. To support clinical decision making, a novel dataset of neuroblastoma organoids is presented including molecular and drug sensitivity features. Future developments will explore these new techniques, as well as liquid biopsies and immunotherapies, to improve the chances of children and young adults with cancer by more accurately diagnosing and treating tumors using precision medicine.