Type 1 IGF receptor associates with adverse outcome and cellular radioresistance in paediatric high-grade glioma.
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Date
2020-03-01ICR Author
Author
Simpson, AD
Soo, YWJ
Rieunier, G
Aleksic, T
Ansorge, O
Jones, C
Macaulay, VM
Type
Journal Article
Metadata
Show full item recordAbstract
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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Subject
Cell Line, Tumor
Humans
Glioma
Brain Neoplasms
DNA Damage
Pyrazoles
Triazines
Receptor, IGF Type 1
Tissue Array Analysis
Immunohistochemistry
Signal Transduction
Radiation Tolerance
Neoplasm Grading
Research team
Glioma Team
Language
eng
Date accepted
2019-11-19
License start date
2020-03
Citation
British journal of cancer, 2020, 122 (5), pp. 624 - 629
Publisher
NATURE PUBLISHING GROUP