MOLECULAR SUBTYPING OF PEDIATRIC MEDULLOBLASTOMA: CLINICAL, PROGNOSTIC, AND THERAPEUTIC IMPLICATIONS
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Medulloblastoma(MB)isthemostcommonmalignantpediatricbraintumorandisnowrecognizedasamolecularlystratifiedspectrumcomprisingfourprincipalsubgroups:WNT,SHH,Group3,andGroup4.Implementationofgenomicandepigenomicprofilingandtheincorporationofsubgroupingintothe2021WHOCNS5classificationhaveclarifiedsubstantialheterogeneityintumorbiology,prognosis,metastaticbehavior,andtherapeuticresponse.However,translatingmolecularunderstandingintodurable,lesstoxictherapiesremainschallenging,particularlyforbiologicallyaggressivediseasesuchasmetastaticGroup3andTP53-mutantSHHtumors.Thisreviewsummarizesmolecularclassificationanddiagnosticalgorithms(includingDNAmethylationprofiling),subgroupbiology,prognosticimplications,currentstandard-of-caretreatmentbysubgroup,andemergingtherapeuticdirectionsincludingpathwayinhibition,epigenetictherapies,drugrepurposing,immunotherapy,andnoveldeliveryapproaches.Persistentbarriers—especiallyblood–brainbarrier(BBB)constraintsandglobalinequitiesinaccesstomoleculardiagnosticsandadvancedradiotherapy—mustbeaddressedtoensurethatprecisionneuro-oncologyimprovesoutcomesandqualityoflifeforchildrenwithmedulloblastomaworldwide
