Clinical and pre-clinical utility of genomics in medulloblastoma

Expert Review of Neurotherapeutics
Carolina Nör, Vijay Ramaswamy

Abstract

Integrated genomics has significantly advanced our understanding of medulloblastoma heterogeneity. It is now clear that it actually comprises at least four distinct molecular subgroups termed Wnt/Wingless (WNT), Sonic Hedgehog (SHH), Group 3, and Group 4 with stark clinical and biological differences. Areas covered: This paper reviews advances in the classification and risk stratification of medulloblastoma, specifically integrating subgroup with clinical and cytogenetic risk factors, with a summary of the potential to lead to more precise therapies. Moreover, the current state of preclinical modeling is summarized with respect to their utility in generating new treatments and correlation with genomic discoveries. Opportunities and challenges in developing new treatment paradigms are summarized and discussed, specifically new therapies for very high-risk metastatic/MYC-amplified Group 3 and TP53-mutant SHH and reductions in therapy for lower risk groups. Expert commentary: Survival across medulloblastoma has been stagnant for over 30 years, and new treatment paradigms are urgently required. Current therapy significantly over treats a high proportion of patients leaving them with lifelong side effects; while many patients still ...Continue Reading

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Citations

Mar 9, 2019·Pediatric Blood & Cancer·Liana NobreVijay Ramaswamy
Sep 11, 2019·Neuro-oncology·Rashad JabarkheelVijay Ramaswamy
Aug 20, 2021·Acta Neuropathologica·Hallie ColtinVijay Ramaswamy
Sep 4, 2020·Pediatric Neurosurgery·Matthew P MullarkeyDavid I Sandberg

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