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Medulloblastoma molecular dissection: the way toward targeted therapy - PubMed

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Review

Medulloblastoma molecular dissection: the way toward targeted therapy

Marc Remke et al. Curr Opin Oncol. 2013 Nov.

Abstract

Purpose of review: The advent of integrated genomics revealed profound insights into medulloblastoma pathogenesis. However, these biological findings have yet to be translated into the clinic, as current treatment comprises surgical resection, conventional irradiation, and chemotherapy resulting in significant long-term sequelae. We sought to highlight the potential areas for targeted therapy based on our new understanding of the subgroup-specific tumor biology.

Recent findings: Recently, four distinct molecular subgroups of medulloblastoma have been identified [WNT (wingless), SHH (sonic hedgehog), Group 3, and Group 4]. Profiling of these subgroups revealed distinct genomic events, several of which represent actionable targets for therapy. Specifically, stratification of patients into their respective subgroups has profound prognostic impact, wherein therapy can be de-escalated in patients with favorable prognosis, and intensified therapy or novel agents can be considered in patients with poor prognosis. Novel subgroup-specific therapies are being explored in clinical trials, particularly for the SHH subgroup. Epigenetic modifiers are also recurrently affected in medulloblastoma suggesting that epigenetic therapy can be considered in a subset of patients.

Summary: The identification of subgroup-specific, actionable therapeutic targets has the potential to revolutionize therapy for medulloblastoma patients, and result in significantly improved quality of life in survivors and improved overall survival.

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