title: SHH inhibitors for the treatment of medulloblastoma.
abstract: Medulloblastoma is the most common malignant brain tumor of childhood. It is currently stratified into four molecular variants through the advances in transcriptional profiling. They include: wingless, sonic hedgehog (SHH), Group III, and Group IV. The SHH group is characterized by constitutive activation of the SHH signaling pathway, and genetically characterized by mutations in patched homolog 1 (PTCH1) or other downstream pathway mutations. SHH inhibitors have become of great clinical interest in treating SHH-driven medulloblastoma. Many inhibitors are currently in different stages of development, some already approved for other SHH-driven cancers, such as basal cell carcinoma. In vitro and in vivo medulloblastoma studies have shown efficacy and these findings have been translated into Phase I and II clinical trials. In this review, we present an overview of SHH medulloblastoma, as well as a discussion of currently available SHH inhibitors, and the challenges associated with their use.
authors.affiliation: Department of Pediatrics, Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: Ayman
authors.initials: A
authors.lastname: Samkari
authors.forename: Jason
authors.initials: J
authors.lastname: White
authors.forename: Roger
authors.initials: R
authors.lastname: Packer
mesh_terms: D000813:Anilides / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002528:Cerebellar Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D008527:Medulloblastoma / Q000188:drug therapy* / Q000378:metabolism; D011725:Pyridines / Q000627:therapeutic use
chemical_list: D000813:Anilides; D000970:Antineoplastic Agents; D053823:Hedgehog Proteins; C538724:HhAntag691; D011725:Pyridines
keywords: basal cell carcinoma; gorlin syndrome; medulloblastoma; smoothened; sonic hedghog; vismodegib