Comparative Drug Response Profiling in Neuroblastoma Cell Lines and Patient-Derived Tumor Organoids.

High-risk neuroblastoma remains a leading cause of pediatric cancer mortality, and improved preclinical models are needed to guide therapeutic developments. We screened seven high-risk neuroblastoma cell lines and three patient-derived tumor organoids with 528 compounds alongside bone marrow controls, and compared them with external datasets. Unsupervised clustering of drug response clearly separated two-dimensional (2D) and three-dimensional (3D) models, with 3D models showing more coherent responses and overall higher drug sensitivity. Mitotic and DNA-damage pathways emerged as key vulnerabilities, and standard-of-care compounds, including doxorubicin, etoposide, and topotecan, were more active in 3D than 2D. This work highlights the potential of 3Dmodels as useful tools for therapy prioritization in neuroblastoma.