{"entity":{"id":"paper-robinson-vismodegib-shh-medulloblastoma-jco-2015","kind":"paper","name":"Vismodegib in recurrent sonic hedgehog-subgroup medulloblastoma (PBTC-025B and PBTC-032)","aka":[],"tldr":"The hedgehog pathway inhibitor vismodegib produced responses in recurrent SHH-subgroup medulloblastoma but not in other subgroups, and only in tumours whose mutation lay upstream of the drug's target, showing that molecular subgrouping must guide its use.","summary":"Two phase 2 studies of vismodegib in 43 patients (adults and children) with recurrent medulloblastoma, analysed by molecular subgroup and mutation.\n\nResponses occurred in 3 of 12 adults and 1 of 8 children with SHH-subgroup tumours and in none of the 20 non-SHH patients; responders had PTCH1 or SMO alterations, while tumours with downstream SUFU or GLI2 alterations did not respond, and growth plate fusion occurred in children.","asOf":"2026-09-17","links":[{"label":"J Clin Oncol 2015","url":"https://doi.org/10.1200/JCO.2014.60.1591"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26169613/"}],"tags":[],"related":[],"cancers":["medulloblastoma-shh"],"sections":[],"technologies":[],"targets":[],"drugs":["vismodegib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2015,"doi":"10.1200/JCO.2014.60.1591","pmid":"26169613","authors":"Robinson GW, Orr BA, Wu G, et al.","paperType":"observational","findings":["Responses only in SHH-subgroup tumours with upstream (PTCH1, SMO) alterations.","No responses in non-SHH medulloblastoma."],"whatItMeans":"Vismodegib or sonidegib is reserved for skeletally mature patients with relapsed SHH medulloblastoma and upstream pathway mutations, a niche defined by this trial.","caveats":["Small numbers; responses were transient.","Irreversible growth plate closure in growing children."],"changedPractice":true,"participants":43},"route":"/key-papers/paper-robinson-vismodegib-shh-medulloblastoma-jco-2015/","neighbours":{"cancer":[{"id":"medulloblastoma-shh","kind":"cancer","name":"SHH-activated medulloblastoma","route":"/cancers/medulloblastoma-shh/"}],"drug":[{"id":"vismodegib","kind":"drug","name":"Vismodegib","route":"/drugs/vismodegib/"}],"journal":[{"id":"jco","kind":"journal","name":"Journal of Clinical Oncology","route":"/journals/jco/"}]}}