From developmental origins to relapse: molecular and therapeutic insights in medulloblastoma.

Medulloblastoma (MB) is the most common malignant pediatric brain tumor. The increasing emphasis in genomic research within recent decades has shined a spotlight on the genomic and epigenetic landscape of this disease. Through methylome and transcriptome data from large MB patient cohorts, four discrete molecular subgroups and their respective subtypes have been identified, each with differing molecular and clinical characteristics. In this review, we outline recent discoveries concerning MB subgroups and subtypes, and how they have informed new epigenetic, radiation, and immunological therapeutic approaches. Although these discoveries have guided the de-escalation of low-risk molecular subgroups, to date, no subgroup-specific therapeutic strategies have been implemented in the clinic. Currently, a paucity of tractable molecular alterations and preclinical models has been a major barrier for the development of meaningful MB therapies. A strong focus on elucidating these gaps in knowledge will allow for the development of tailored therapies for high-risk MB and metastatic recurrence.