title: The rationale for targeted therapies in medulloblastoma.
abstract: Medulloblastoma (MB) is the most frequent malignant brain tumor in children. Patients with MB who are classified as having high-risk disease or those with recurrent disease respond poorly to current therapies and have an increased risk of MB-related mortality. Preclinical studies and molecular profiling of MB tumors have revealed upregulation or activation of several key signaling pathways such as the sonic hedgehog and WNT pathways. Although the exact mechanisms underlying MB tumorigenesis remain poorly understood, inhibiting these key pathways with molecularly targeted therapies represents an important approach to improving MB outcomes. Several molecularly targeted therapies are already under clinical investigation in MB patients. We discuss current preclinical and clinical data, as well as data from clinical trials of targeted therapies that are either ongoing or in development for MB.
authors.affiliation: Corresponding author: Robert C. Castellino, MD, Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Department of Pediatrics, Emory University School of Medicine, Health Sciences Research Building, 1760 Haygood Drive NE, Room E394, Atlanta, GA 30322. rccaste@emory.edu.
authors.forename: Tobey J
authors.initials: TJ
authors.lastname: MacDonald
authors.forename: Dolly
authors.initials: D
authors.lastname: Aguilera
authors.forename: Robert C
authors.initials: RC
authors.lastname: Castellino
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002528:Cerebellar Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D008527:Medulloblastoma / Q000188:drug therapy* / Q000378:metabolism; D058990:Molecular Targeted Therapy; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors*; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D009363:Neoplasm Proteins
keywords: hedgehog; medulloblastoma; oncogenic signaling; smoothened; targeted therapy