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

European journal of cancer (Oxford, England : 1990) [Eur J Cancer] 2025 Mar 11; Vol. 218, pp. 115275. Date of Electronic Publication: 2025 Feb 08.

Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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). Cell lines, NBL-PDOs and their parental tumors were characterized utilizing (lc)WGS, WES and RNAseq. Cells were exposed to ∼200 compounds. Results were transferred to the R2 visualization platform.
Results: A powerful reference set of cell lines is available, reflecting distinct known pharmacologic vulnerabilities. HTS identified additional therapeutic vulnerabilities, such as a striking correlation between a positive mesenchymal signature and sensitivity to BCL2-inhibitor venetoclax. Finally, we explored personalized drug sensitivities within iTHER, demonstrating HTS can support genomic and transcriptomic results, thereby strengthening the rationale for clinical uptake.
Conclusion: We established a dynamic publicly available dataset with detailed genomic, transcriptomic, and pharmacological annotation of classical neuroblastoma cell lines as well as novel sharable NBL-PDOs, representing the heterogeneous landscape of neuroblastoma. We anticipate that in vitro drug screening will be complementary to genomic-guided precision medicine by supporting clinical decision making, thereby improving prognosis for all neuroblastoma patients in the future.
(Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

English

Publisher: Elsevier Science Ltd Country of Publication: England NLM ID: 9005373 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0852 (Electronic) Linking ISSN: 09598049 NLM ISO Abbreviation: Eur J Cancer Subsets: MEDLINE

Neuroblastoma*/drug therapy , Neuroblastoma*/genetics , Neuroblastoma*/pathology , Precision Medicine*/methods , Organoids*/drug effects , Organoids*/pathology , High-Throughput Screening Assays*/methods , Antineoplastic Agents*/pharmacology, Humans ; Cell Line, Tumor ; Drug Screening Assays, Antitumor/methods ; Transcriptome ; Gene Expression Profiling

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