Abstract 532: Single-cell analysis reveals neuroblastoma heterogeneity and therapeutic opportunities

Abstract Neuroblastoma is the most common extracranial tumor found in neonatal patients, arising from neural crest cells. By utilizing specific Neuroblastoma cell lines, we have developed clones that express the non-coding RNA NDM29. These investigations have enabled the assessment of NDM29's role in tumor differentiation, identifying new therapeutic targets for controlling tumor malignancy. Further studies highlighted the presence of different cell subpopulations in this model by performing a single-cell sequencing analysis. These subpopulations were isolated with FACS analysis. The cellular heterogeneity characterizing this model reflects what is observed in patients. The gene expression of potential therapeutic targets identified in the heterogeneous model was evaluated in individual subpopulations. The individual subpopulations were pharmacologically treated by inhibiting some of these targets. These treatments revealed subpopulations that were either more sensitive or more resistant to specific inhibitors. By performing gene ontology analyses using sequencing data, we identified potential new pharmacological targets to enhance the mortality of even the resistant cells. Citation Format: Michele Tomanelli, Jennifer Hoti, Matteo Saettone, Daniele Reverberi, Adriana Bajetto, Tullio Florio, Aldo Pagano. Single-cell analysis reveals neuroblastoma heterogeneity and therapeutic opportunities [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 532.