Abstract
Bolstered by technology that allows for extensive and rapid genomic interrogation, the scientific literature has exploded with reports on the molecular composition of medulloblastoma. This influx of information has redefined medulloblastoma as a heterogeneous disease comprised of vastly different subtypes. Although the current consensus is that medulloblastoma has four general molecular subtypes (WNT, SHH, Group 3, and Group 4) [1], key questions remain: Are these four subtypes the most clinically relevant? Do more subtypes, or even subdivisions within subtypes, exist that will impact therapy? Clinical trials are being designed to address these questions, but current therapeutic options lag far behind the blistering pace set by recent scientific discoveries. Predictably, as more targeted therapies become available, disease subtyping and genomic interrogation of each tumor will become even more crucial to patient care. The problem that oncologists currently face is what is clinically relevant today, and what will be relevant in the immediate future? Clinically, the identification of the SHH and WNT subtypes of medulloblastoma is poised to have the most immediate impact. Targeted inhibitors of the SHH pathway, which are currently in Phase 2 trials (NCT00939484, NCT01125800, NCT01601184), are promising agents for treating SHH medulloblastoma. Therefore, knowing a tumor is of the SHH subtype is immediately useful to the clinician seeking therapeutic options for a patient with relapsed disease. With an overall survival greater than 90% on current clinical trials, patients with WNT medulloblastoma have the best outcome [2,3]. It is widely believed that reduced-intensity therapy, which would decrease the risk of therapy-related morbidity, can be administered to this population without compromising their outcome. Clinical trials of reduced therapy for WNT medulloblastomaarebeingdeveloped;thus,pretreatmentidentificationofWNT
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