New research directions in medulloblastoma

Medulloblastoma is the most common type of pediatric malignant brain tumor where the most important amount of clinical and radiological data has been accumulated in recent years. This has led to its sophistication in the management of these patients with a clear benefit for the patients. Long-term outcome and sequelae have been described and their causes well understood such as preventive measures which can now be implemented.

This review paper does not attempt to make a systematic review of the literature in the field of research regarding medulloblastoma. It rather reflects more the opinion of a pediatric oncological team involved for a long time in this type of research. Therefore, a relevant literature review was carried out and selected by the senior author.

Medulloblastoma is no longer a single entity but a group of at least 4 different diseases with a specific oncogenesis. In addition, biomarkers for prognosis have emerged to complement the known clinico-radiological risk factors. If this biological classification has allowed to modulate the therapeutic strategies, it has not yet brought many new drugs (except for the Sonic Hedgehog inhibitors) in the armamentarium against medulloblastomas. Consequently, some high-risk tumors remain difficult to cure. Combining data on oncogenesis and prognostic biomarkers will allow to define risk groups more specifically. New targeted therapies that are more effective and less toxic are desperately needed. Alternatively, it is also justified to study preventive measures to decrease the sequelae of the tumor and its treatments. From the therapeutic point of view, we scarcely know the biological determinants of chemosensitivity and radiosensitivity, as well as those associated with metastases which are indeed invaluable for tailored therapeutic strategies.

If some genetic causes of medulloblastoma are known, the occurrence of the disease is largely unexplained for the others, justifying more research in this area. If genomics (and to a lesser extent epigenomics) of these neoplasms has been well studied, little is known on their proteomics and on the regulatory networks involved in the biological behavior of these tumor cells. New models are developed to test these aspects.