SHH pathway inhibition is protumourigenic in adamantinomatous craniopharyngioma

Journal article


Publication Details

Author(s): Carreno G, Boult JKR, Apps J, Gonzalez-Meljem JM, Haston S, Guiho R, Stache C, Danielson LS, Koers A, Smith LM, Virasami A, Panousopoulos L, Buchfelder M, Jacques TS, Chesler L, Robinson SP, Martinez-Barbera JP
Journal: Endocrine-Related Cancer
Publication year: 2019
Volume: 26
Journal issue: 3
Pages range: 355-366
ISSN: 1351-0088


Abstract

Pharmacological 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 magnetic resonance imaging (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.


FAU Authors / FAU Editors

Buchfelder, Michael Prof. Dr.
Lehrstuhl für Neurochirurgie


External institutions with authors

Great Ormond Street Hospital for Children NHS Foundation Trust
The Institute of Cancer Research (ICR)
University College London (UCL)


How to cite

APA:
Carreno, G., Boult, J.K.R., Apps, J., Gonzalez-Meljem, J.M., Haston, S., Guiho, R.,... Martinez-Barbera, J.P. (2019). SHH pathway inhibition is protumourigenic in adamantinomatous craniopharyngioma. Endocrine-Related Cancer, 26(3), 355-366. https://dx.doi.org/10.1530/ERC-18-0538

MLA:
Carreno, G., et al. "SHH pathway inhibition is protumourigenic in adamantinomatous craniopharyngioma." Endocrine-Related Cancer 26.3 (2019): 355-366.

BibTeX: 

Last updated on 2019-19-03 at 01:08