Medulloblastoma is the most common malignant brain cancer in children, and most frequently arises in the cerebellum [1-3]. Molecular profiling has allowed their classification into four subgroups: Wingless (WNT), Sonic Hedgehog (SHH), Group 3, and Group 4 [4,5]. Although the 5-year survival for medulloblastoma is around 72%, retrospective studies show that long-term outcomes are subgroup-specific. WNT sub-group patients have a better prognosis with a 5-year survival rate of more than 90% [6]. Group 3 and Group 4 medulloblastoma patients have a 5-year survival rate of 40-60% and 75-80%, respectively. The survival of SHH-medulloblastoma patients is defined by the p53 status of their tumors, with p53 mutations (SHH-1) driving down survival to 41%, in contrast to a 5-year survival of 81% in patients with wild type p53 (SHH-2) [6,7]. Based on multivariate analysis, it is accepted that p53 status is the most important risk factor for children with SHH-1 medulloblastoma, with 76% of deaths associated with p53 mutations or loss of function [7]. Despite this intertumoral survival heterogeneity, current treatments for all medulloblastomas include surgical resection, craniospinal radiation therapy, and multiagent chemotherapy. Survival has certainly improved, however, recurrence, metastasis and long-term cognitive deficits due to treatment-related toxicity to the normal brain continue to be major clinical challenges [8]. Therefore, a better understanding of tumor biology will allow a more targeted treatment approach and spare the normal brain. Here, we focus our discussions on molecular differences in tumor vasculature between the medulloblastoma subgroups, and how variability in their structure and architecture may influence survival and therapeutic responses.
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