Abstract
Recent advances in cancer genomics have revolutionized the characterization and classification of medulloblastomas. According to the current WHO guidelines, medulloblastomas are now classified into the following molecularly defined groups: Wnt signaling pathway (WNT)-activated, sonic hedgehog signaling pathway (SHH)-activated and tumor suppressor protein p53 (TP53)-mutant, SHH-activated and TP53-wildtype, and non-WNT/non-SHH (i.e. group 3 and group 4). Importantly, genomic, epigenomic, and proteomic advances have created a potential paradigm shift in therapeutic options. The challenge now is to (i) translate these observations into new therapeutic approaches and (ii) employ these observations in clinical practice, utilizing the classification following a molecular analysis for diagnosis and application of new subgroup-specific targeted therapeutics.
Highlights
Medulloblastomas account for 12% of childhood brain tumors[1]
Recent advances in cancer genomics have led to a fundamental change in medulloblastoma classification
A Pediatric Brain Tumor Consortium study evaluated the use of GDC-0449, which blocks a key protein (Smoothened, or SMO) in the sonic hedgehog (SHH) signaling pathway in medulloblastoma, and, as anticipated, patients with the SHH subtype who had the SMO/PTCH mutation responded to this drug[12]
Summary
Medulloblastomas account for 12% of childhood brain tumors[1]. Approximately 80% of medulloblastomas occur in children under the age of 15. Keywords Medulloblastoma, specific targeted therapeutics, WNT, SHH, TP53 version 1 published 13 Apr 2017 CTNNB1, catenin beta 1; DDX3X, DEAD-box helicase 3; Lmx1a, LIM homeobox transcription factor; PTCH1, Patched-1; SHH, sonic hedgehog; SMARCA4, SWI (switching)/SNF (sucrose non-fermenting)-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4; SMO, smoothened receptor; SUFU, suppressor of fused homolog protein; TERT, telomerase reverse transcriptase; TGF-β, transforming growth factor beta; TP53, tumor suppressor protein p53.
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