Neuroblastoma Organoids and Cell Lines Show Distinct Drug-Response Profiles
A 528-compound screen compared seven high-risk neuroblastoma cell lines with three patient-derived tumor organoids and bone marrow controls. The model formats separated by their response profiles.
Comparing Two-Dimensional and Three-Dimensional Models
A Karolinska Institutet-led team compared drug responses in seven high-risk neuroblastoma cell lines and three patient-derived tumor organoids. The screen tested 528 compounds, included bone marrow controls and compared the findings with external datasets. This design examined whether model format changes the patterns detected in a broad pharmacological screen.
Unsupervised clustering separated the two-dimensional cell lines from the three-dimensional organoids. The organoid models showed more coherent response patterns and, overall, greater drug sensitivity in the comparisons reported. Thus, the two formats produced distinguishable pharmacological profiles within the same investigation.
Drug Classes with Activity in the Organoid Models
Compounds affecting mitosis and DNA-damage pathways emerged as important vulnerabilities. Standard-of-care agents, including doxorubicin, etoposide and topotecan, were more active in the three-dimensional models than in the cell lines. The bone marrow controls gave the screen a separate reference for assessing responses outside the tumor models.
The comparison supports further investigation of organoids for treatment prioritization in neuroblastoma and shows how a model panel can influence the drug classes highlighted by screening. The organoid component comprised three models, and the study's overall format comparison should be interpreted with that composition in view.