Targeting MYC in High-Risk Medulloblastoma

Medulloblastoma is the most common malignant brain tumor in children. Group 3 medulloblastoma (G3 MB) represents the most aggressive molecular subtype and is associated with poor prognosis, particularly in cases characterized by high expression or amplification of the MYC oncogene. Current treatment strategies are not tailored to this subgroup and are associated with significant long-term toxicities, highlighting the need for more specific therapeutic approaches. This study aims to characterize biological processes and molecular pathways driven by high MYC expression in high-risk G3 medulloblastoma in order to identify potential therapeutic vulnerabilities. The study will investigate MYC-associated regulation of gene expression and RNA splicing in tumor cells and will define molecular dependencies that may be targeted using candidate or repurposed anticancer agents. To achieve this, publicly available genomic datasets will be analyzed, findings will be validated in patient tumor specimens, and patient-derived three-dimensional (3D) tumor models will be established from surgical samples. These models will be used for ex vivo assessment of selected therapeutic strategies in a system that preserves key features of the original tumor. This translational approach integrates computational analyses, molecular validation, and functional testing in patient-derived models to improve understanding of MYC-associated tumor biology in Group 3 medulloblastoma.

Inclusion Criteria: * Patients with histologically confirmed Group 3 medulloblastoma (G3 MB) * Age between 0 and 20 years * Undergoing surgical treatment at the UOC Child Neurosurgery Unit, Fondazione Policlinico Universitario "A. Gemelli", IRCCS, Rome * Availability of tumor tissue obtained during standard-of-care surgical resection for molecular analyses and/or establishment of patient-derived organoids * Written informed consent provided by the patient and/or parent/legal guardian (prospective cohort) * Inclusion of retrospective cases in accordance with applicable Italian privacy regulations (Art. 110-bis) Exclusion Criteria: * None