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Radiation Oncology
Published in: Radiation Oncology 1/2017

Open Access 01-12-2017 | Research

Predictive biomarkers of resistance to hypofractionated radiotherapy in high grade glioma

Authors: Julian Biau, Emmanuel Chautard, Leanne De Koning, Frank Court, Bruno Pereira, Pierre Verrelle, Marie Dutreix

Published in: Radiation Oncology | Issue 1/2017

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Abstract

Background

Radiotherapy plays a major role in the management of high grade glioma. However, the radioresistance of glioma cells limits its efficiency and drives recurrence inside the irradiated tumor volume leading to poor outcome for patients. Stereotactic hypofractionated radiotherapy is one option for recurrent high grade gliomas. Optimization of hypofractionated radiotherapy with new radiosensitizing agents requires the identification of robust druggable targets involved in radioresistance.

Methods

We generated 11 xenografted glioma models: 6 were derived from cell lines (1 WHO grade III and 5 grade IV) and 5 were patient derived xenografts (2 WHO grade III and 3 grade IV). Xenografts were treated by hypofractionated radiotherapy (6x5Gy). We searched for 89 biomarkers of radioresistance (39 total proteins, 26 phosphoproteins and 24 ratios of phosphoproteins on total proteins) using Reverse Phase Protein Array.

Results

Both type of xenografted models showed equivalent spectrum of sensitivity and profile of response to hypofractionated radiotherapy. We report that Phospho-EGFR/EGFR, Phospho-Chk1/Chk1 and VCP were associated to resistance to hypofractionated radiotherapy.

Conclusions

Several compounds targeting EGFR or CHK1 are already in clinical use and combining them with stereotactic hypofractionated radiotherapy for recurrent high grade gliomas might be of particular interest.
Appendix
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Metadata
Title
Predictive biomarkers of resistance to hypofractionated radiotherapy in high grade glioma
Authors
Julian Biau
Emmanuel Chautard
Leanne De Koning
Frank Court
Bruno Pereira
Pierre Verrelle
Marie Dutreix
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Radiation Oncology / Issue 1/2017
Electronic ISSN: 1748-717X
DOI
https://doi.org/10.1186/s13014-017-0858-0

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