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dc.contributor.authorCarreno, G
dc.contributor.authorBoult, JKR
dc.contributor.authorApps, J
dc.contributor.authorGonzalez-Meljem, JM
dc.contributor.authorHaston, S
dc.contributor.authorGuiho, R
dc.contributor.authorStache, C
dc.contributor.authorDanielson, LS
dc.contributor.authorKoers, A
dc.contributor.authorSmith, LM
dc.contributor.authorVirasami, A
dc.contributor.authorPanousopoulos, L
dc.contributor.authorBuchfelder, M
dc.contributor.authorJacques, TS
dc.contributor.authorChesler, L
dc.contributor.authorRobinson, SP
dc.contributor.authorMartinez-Barbera, JP
dc.date.accessioned2019-01-25T09:55:15Z
dc.date.issued2019-03-01
dc.identifier.citationEndocrine-related cancer, 2019, 26 (3), pp. 355 - 366
dc.identifier.issn1351-0088
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3024
dc.identifier.eissn1479-6821
dc.identifier.doi10.1530/erc-18-0538
dc.description.abstractPharmacological inhibition of the sonic hedgehog (SHH) pathway can be beneficial against certain cancers but detrimental in others. Adamantinomatous craniopharyngioma (ACP) is a relevant pituitary tumour, affecting children and adults, that is associated with high morbidity and increased mortality in long-term follow-up. We have previously demonstrated overactivation of the SHH pathway in both human and mouse ACP. Here, we show that this activation is ligand dependent and induced by the expression of SHH protein in a small proportion of tumour cells. We investigate the functional relevance of SHH signalling in ACP through MRI-guided preclinical studies using an ACP mouse model. Treatment with vismodegib, a clinically approved SHH pathway inhibitor, results in a significant reduction in median survival due to premature development of highly proliferative and vascularised undifferentiated tumours. Reinforcing the mouse data, SHH pathway inhibition in human ACP leads to a significant increase in tumour cell proliferation both ex vivo, in explant cultures, and in vivo, in a patient-derived xenograft model. Together, our results demonstrate a protumourigenic effect of vismodegib-mediated SHH pathway inhibition in ACP.
dc.formatPrint
dc.format.extent355 - 366
dc.languageeng
dc.language.isoeng
dc.publisherBIOSCIENTIFICA LTD
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectAnimals
dc.subjectHumans
dc.subjectMice
dc.subjectCraniopharyngioma
dc.subjectPituitary Neoplasms
dc.subjectDisease Models, Animal
dc.subjectSignal Transduction
dc.subjectCell Proliferation
dc.subjectAdolescent
dc.subjectChild
dc.subjectChild, Preschool
dc.subjectMale
dc.subjectHedgehog Proteins
dc.titleSHH pathway inhibition is protumourigenic in adamantinomatous craniopharyngioma.
dc.typeJournal Article
dcterms.dateAccepted2019-01-15
rioxxterms.versionofrecord10.1530/erc-18-0538
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2019-03
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfEndocrine-related cancer
pubs.issue3
pubs.notesNo embargo
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Paediatric Solid Tumour Biology and Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Paediatric Solid Tumour Biology and Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Paediatric Solid Tumour Biology and Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Pre-Clinical MRI
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Paediatric Solid Tumour Biology and Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Paediatric Solid Tumour Biology and Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Paediatric Solid Tumour Biology and Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Pre-Clinical MRI
pubs.publication-statusPublished
pubs.volume26
pubs.embargo.termsNo embargo
icr.researchteamPaediatric Solid Tumour Biology and Therapeutics
icr.researchteamPre-Clinical MRI
dc.contributor.icrauthorBoult, Jessica
dc.contributor.icrauthorChesler, Louis
dc.contributor.icrauthorRobinson, Simon


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