Radiation-induced neuroinflammation: a potential protective role for poly(ADP-ribose) polymerase inhibitors?

Gutierrez-Quintana, R. , Walker, D. J. , Williams, K. J., Forster, D. M. and Chalmers, A. J. (2022) Radiation-induced neuroinflammation: a potential protective role for poly(ADP-ribose) polymerase inhibitors? Neuro-Oncology Advances, 4(1), vdab190. (doi: 10.1093/noajnl/vdab190) (PMID:35118383) (PMCID:PMC8807076)

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Radiotherapy (RT) plays a fundamental role in the treatment of glioblastoma (GBM). GBM are notoriously invasive and harbor a subpopulation of cells with stem-like features which exhibit upregulation of the DNA damage response (DDR) and are radioresistant. High radiation doses are therefore delivered to large brain volumes and are known to extend survival but also cause delayed toxicity with 50%–90% of patients developing neurocognitive dysfunction. Emerging evidence identifies neuroinflammation as a critical mediator of the adverse effects of RT on cognitive function. In addition to its well-established role in promoting repair of radiation-induced DNA damage, activation of poly(ADP-ribose) polymerase (PARP) can exacerbate neuroinflammation by promoting secretion of inflammatory mediators. Therefore, PARP represents an intriguing mechanistic link between radiation-induced activation of the DDR and subsequent neuroinflammation. PARP inhibitors (PARPi) have emerged as promising new agents for GBM when given in combination with RT, with multiple preclinical studies demonstrating radiosensitizing effects and at least 3 compounds being evaluated in clinical trials. We propose that concomitant use of PARPi could reduce radiation-induced neuroinflammation and reduce the severity of radiation-induced cognitive dysfunction while at the same time improving tumor control by enhancing radiosensitivity.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Gutierrez Quintana, Mr Rodrigo and Chalmers, Professor Anthony and Walker, Dr David
Authors: Gutierrez-Quintana, R., Walker, D. J., Williams, K. J., Forster, D. M., and Chalmers, A. J.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
Journal Name:Neuro-Oncology Advances
Publisher:Oxford University Press
ISSN (Online):2632-2498
Published Online:06 January 2022
Copyright Holders:Copyright © 2022 The Authors
First Published:First published in Neuro-Oncology Advances 4(1): vdab190
Publisher Policy:Reproduced under a Creative Commons Licence

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
306407Glasgow RadNet CentreAnthony ChalmersCancer Research UK (CRUK)C16583/A28803CS - Clinical Trials Research