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

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    Authors
    Gutierrez-Quintana, R.
    Walker, D. J.
    Williams, K. J.
    Forster, D. M.
    Chalmers, A. J.
    Affiliation
    Institute of Cancer Sciences, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK. Division of Pharmacy and Optometry, School of Health Sciences, Manchester Cancer Research Centre, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK. Division of Informatics, Imaging and Data Sciences, Manchester Molecular Imaging Centre, The University of Manchester, Manchester, UK.
    Issue Date
    2022
    
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    Abstract
    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.
    Citation
    Gutierrez-Quintana R, Walker DJ, Williams KJ, Forster DM, Chalmers AJ. Radiation-induced neuroinflammation: a potential protective role for poly(ADP-ribose) polymerase inhibitors?. Vol. 4, Neuro-Oncology Advances. Oxford University Press (OUP); 2022.
    Journal
    Neuro-Oncology Advances
    URI
    http://hdl.handle.net/10541/625088
    DOI
    10.1093/noajnl/vdab190
    PubMed ID
    35118383
    Additional Links
    https://dx.doi.org/10.1093/noajnl/vdab190
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1093/noajnl/vdab190
    Scopus Count
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    All Paterson Institute for Cancer Research

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