Exploring high-throughput drug sensitivity testing in neuroblastoma cell lines and patient-derived tumor organoids in the era of precision medicine.

Introduction: Despite druggable events to be present in 80 % of neuroblastomapatients within the Princess Máxima Center precision medicine program 'iTHER', clinical uptake of treatment recommendations has been low, and the clinical impact for individual patients remains hard to predict. This stresses the need for a method integrating genomics and transcriptomics with functional approaches into therapeutic decision making.

Methods: We aimed to launch an online repository integrating genomics and transcriptomics with high-throughput drug screening (HTS) of nineteen commonly used neuroblastoma cell lines and fifteen neuroblastoma patient-derived organoids (NBL-PDOs).

Blocking MIF secretion enhances CAR T-cell efficacy against neuroblastoma.

Introduction: Chimeric antigen receptor (CAR) T-cell therapy is a promising and innovative cancer therapy. However, immunosuppressive tumor microenvironments (TME) limit T cell persistence and durable efficacy. Here, we aimed to identify and target immunosuppressive factors in the TME of neuroblastoma, a pediatric extracranial solid tumor, to improve CAR-T efficacy.

Implementation of paediatric precision oncology into clinical practice: The Individualized Therapies for Children with cancer program 'iTHER'.

iTHER is a Dutch prospective national precision oncology program aiming to define tumour molecular profiles in children and adolescents with primary very high-risk, relapsed, or refractory paediatric tumours. Between April 2017 and April 2021, 302 samples from 253 patients were included. Comprehensive molecular profiling including low-coverage whole genome sequencing (lcWGS), whole exome sequencing (WES), RNA sequencing (RNA-seq), Affymetrix, and/or 850k methylation profiling was successfully performed for 226 samples with at least 20% tumour content.