Abstract #1509

Using MRI to assess sonic hedgehog pathway inhibition in a genetically-engineered mouse model of adamantinomatous craniopharyngioma

Jessica K.R. Boult¹, Gabriela Carreno², John R. Apps², Laura S. Danielson³, Laura M. Smith³, Alexander Koers³, Louis Chesler³, Juan Pedro Martinez-Barbera², and Simon P. Robinson¹

¹Division of Radiotherapy and Imaging, The Institute of Cancer Research, London, United Kingdom, ²Developmental Biology and Cancer Research Programme, Birth Defects Research Centre, Great Ormond Street Institute of Child Health, University College London, London, United Kingdom, ³Division of Clinical Studies, The Institute of Cancer Research, London, United Kingdom

Expression of sonic hedgehog (SHH) pathway components is enriched in adamantinomatous craniopharyngiomas (ACPs) arising in Hesx1^Cre/+;Ctnnb1^lox(ex3)/+ mice compared to control pituitaries. An MRI-embedded trial of smoothened inhibitor vismodegib in this genetically-engineered mouse model was undertaken to assess SHH pathway inhibition in ACP. Longitudinal MRI identified accelerated solid tumour growth in response to 28 days vismodegib treatment, which was associated with increased tumour cell proliferation, and resulted in shorter survival. 7 days of treatment induced early tumoural lesions in Hesx1^Cre/+;Ctnnb1^lox(ex3)/+ pituitaries, resulted in a more undifferentiated and proliferative phenotype, and was associated with an elevated number of cells with clonogenic potential.

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