Targeting MYC in High-Risk Medulloblastoma

Condition(s) studied

Investigational drug(s) / intervention(s)

Tumor tissue collection: Tumor tissue will be collected during standard-of-care surgical resection of medulloblastoma. No additional surgical procedures will be performed for research purposes. Collected tissue will be used for molecular analyses and the establishment of patient-derived three-dimensional (3D) cultures for ex vivo translational research, including characterization of MYC-associated molecular pathways and evaluation of tumor cell responses to selected compounds in preclinical assays.

Study summary

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.

Eligibility

Primary outcome measure(s)

• Successful establishment of patient-derived organoids (PDOs) from medulloblastoma surgical specimens — Up to 24 months
  Rate of successful generation of patient-derived organoids (PDOs) from freshly resected high-risk Group 3 medulloblastoma surgical specimens. Success will be defined by the ability of tumor samples to generate stable and expandable three-dimensional (3D) cultures in vitro. Established models will be evaluated for histological and molecular concordance with the corresponding parental tumors using standard pathological and genetic analyses.

Trial sites (1)

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