Type 1 IGF receptor associates with adverse outcome and cellular radioresistance in paediatric high-grade glioma.

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ID: 103988
2020
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Abstract
High-grade glioma (HGG) is highly resistant to therapy, prompting us to investigate the contribution of insulin-like growth factor receptor (IGF-1R), linked with radioresistance in other cancers. IGF-1R immunohistochemistry in 305 adult HGG (aHGG) and 103 paediatric/young adult HGG (pHGG) cases revealed significant association with adverse survival in pHGG, with median survival of 13.5 vs 29 months for pHGGs with moderate/strong vs negative/weak IGF-1R (p = 0.011). Secondly, we tested IGF-1R inhibitor BMS-754807 in HGG cells, finding minimal radiosensitisation of 2/3 aHGG cell lines (dose enhancement ratios DERs < 1.60 at 2-8 Gy), and greater radiosensitisation of 2/2 pHGG cell lines (DERs ≤ 4.16). BMS-754807 did not influence radiation-induced apoptosis but perturbed the DNA damage response with altered induction/resolution of γH2AX, 53BP1 and RAD51 foci. These data indicate that IGF-1R promotes radioresistance in pHGG, potentially contributing to the association of IGF-1R with adverse outcome and suggesting IGF-1R as a candidate treatment target in pHGG.
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simpson2020typebritish Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Aaron D Simpson, Ying Wei Jenetta Soo, Guillaume Rieunier, Tamara Aleksic, Olaf Ansorge, Chris Jones, Valentine M Macaulay
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Journal British Journal of Cancer
Year 2020
DOI
10.1038/s41416-019-0677-1
URL
Keywords
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