To study neuroblastoma and develop effective treatments, researchers rely on different model systems. The most widely used models of neuroblastoma include transgenic mouse models, cancer cell lines, patient-derived neuroblastoma spheroid cultures and human induced pluripotent stem cell-derived 2D neural crest models. Developing human-relevant model systems is of high importance due to the differences in early sympathoblast development between humans and rodents, which can lead to inaccurate findings. Among the human models patient-derived tumor spheroids stand out due to their three-dimensional structure which resembles real tumors more closely than 2D cultures. However, patient-derived tumor spheroids show high variability between samples and cannot produce standardized cultures for large-scale drug testing.
While all state-of-the-art models offer critical insights, the establishment of a reproducible and scalable, human-relevant, complex (3D) model system for drug screening applications could lead to the discovery of novel, more-effective therapies for high-risk neuroblastoma patients. The NeuroblastORG project addressed this gap by developing a neuroblastoma organoid model, combining both MYCN-overexpressing tumor cells and healthy neural crest cells within a 3D tissue-like structure. These organoids can be generated in large quantities with high reproducibility, making them a powerful tool for testing new treatments and studying the earliest stages of high-risk neuroblastoma formation.
The NeuroblastORG project delivered a novel, patentable technology. This allowed the ERA fellow to get trained in the patenting process. As a result, the patent application has been submitted, and a Hungarian company expressed interest in licensing the patent and offering the platform as a screening service for new compounds developed by pharmaceutical companies.
Following the patenting process, the organoid model will be published to share its full characterization, detailing how well it replicates the molecular features of MYCN-amplified neuroblastoma and paving the way for future drug development efforts. Another publication describing a novel way for delaying therapy resistance was already published as part of the NeuroblastORG project. Additionally, the ERA fellow presented her work at two international conferences as invited speaker and at public events such as the Researcher’s Night and Neuroblastoma Awareness Day. These opportunities greatly strengthened the science communication skills of the ERA fellow.
During the NeuroblastORG project the ERA fellow was able to establish the Human Organoid Laboratory at the HUN-REN Research Centre for Natural Sciences and together with her team they will continue to investigate chemoresistance mechanisms developing within the neuroblastoma organoids upon chemotherapy.
