Establishment and Characterization of Medulloblastoma and Ependymoma Tumoroid Models for Preclinical Research

Abstract

Pediatric brain tumors, particularly medulloblastoma (MB) and ependymoma (EPN), are currently one of the leading causes of cancer-related death in children. Current therapeutic approaches often result in recurrence and long-term complications. To address this limitations, preclinical models have been developed; however, they often do not represent the entire molecular landscape of all subgroups of MB and EPN. Most recently, cancer research has been transformed by organoid technology by allowing the establishment of 3D cell cultures, derived from dissected tissues, such as patient or PDX tumors (tumoroids). In this study, we established and characterized tumoroid models of MB SHH and G3 subgroups. We also attempted to optimize the protocol for establishment of long-term tumoroid culturing of EPN PFA. We confirmed our MB tumoroids maintained their epigenetic profile and subgroup specific signatures through long-term culture. We also validated the potential of these models for preclinical research, by performing high throughput compound screening to identify drug vulnerabilities.