Molecular Targeted Therapies: Time for a Paradigm Shift in Medulloblastoma Treatment?

SIMPLE SUMMARY: In the last decade, medulloblastoma entered the molecular era, with progressive advances in the knowledge of the molecular biology of this rare tumor. These expanding data have allowed the recognition of four distinct molecular subgroups, and, subsequently, the design of novel clinical trials to update the treatment protocols adopted so far, with the introduction of new molecular targeted drugs. ABSTRACT: Medulloblastoma is a rare malignancy of the posterior cranial fossa. Although until now considered a single disease, according to the current WHO classification, it is a heterogeneous tumor that comprises multiple molecularly defined subgroups, with distinct gene expression profiles, pathogenetic driver alterations, clinical behaviors and age at onset. Adult medulloblastoma, in particular, is considered a rarer “orphan” entity in neuro-oncology practice because while treatments have progressively evolved for the pediatric population, no practice-changing prospective, randomized clinical trials have been performed in adults. In this scenario, the toughest challenge is to transfer the advances in cancer genomics into new molecularly targeted therapeutics, to improve the prognosis of this neoplasm and the treatment-related toxicities. Herein, we focus on the recent advances in targeted therapy of medulloblastoma based on the new and deeper knowledge of disease biology.