Genetics of medulloblastoma: clues for novel therapies

Abstract

Medulloblastoma is the most common malignant brain tumor in children. Current medulloblastoma therapy entails surgery, radiation and chemotherapy. The 5-year survival rate for patients ranges from 40 to 70%, with most survivors suffering from serious long-term treatment-related sequelae. Additional research on the molecular biology and genetics of medulloblastoma is needed to identify robust prognostic markers for disease-risk stratification, to improve current treatment regimes and to discover novel and more effective molecular-targeted therapies. Recent advances in molecular biology have led to the development of powerful tools for the study of medulloblastoma tumorigenesis, which have revealed new insights into the molecular underpinnings of this disease. Here we discuss the signaling pathway alterations implicated in medulloblastoma pathogenesis, the techniques used in molecular profiling of these tumors and recent molecular subclassification schemes. Particular emphasis is given to the identification of novel molecular targets for less toxic, patient-tailored therapeutic approaches.

Keywords::

• cerebellar development
• genetics
• hereditary cancer syndromes
• medulloblastoma
• novel therapies
• pediatric
• prognostic marker
• signaling pathway

Financial & competing interests disclosure

This work was supported by grants from the Canadian Cancer Society, Canadian Cancer Society Research Insitute (formerly National Cancer Institute of Canada; 019073), the Pediatric Brain Tumor Foundation USA, the Wiley Fund at the Hospital for Sick Children and b.r.a.i.nchild. James Rutka is a scientist of the Canadian Institutes of Health Research. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.