Fok, Matthew 
ORCID: 0000-0003-4091-6569, Hill, Rhianna, Fowler, Hayley, Clifford, Rachael, Kler, Aaron, Uzzi-Daniel, Jayanma, Rocha, Sonia, Grundy, Gabrielle ORCID: 0000-0003-1506-3664, Parsons, Jason and Vimalachandran, Dale ORCID: 0000-0001-5817-8969
(2023)
Enhancing radiotherapy outcomes in rectal cancer: A systematic review of targeting hypoxia-induced radioresistance.
Clinical and Translational Radiation Oncology, 44.
p. 100695.
Abstract
<h4>Introduction</h4>Neoadjuvant radiotherapy is successfully used in rectal cancer to improve overall survival. However, treatment response is both unpredictable and variable. There is strong evidence to show that the phenomenon of tumour hypoxia is associated with radioresistance, however the mechanism(s) behind this are poorly understood. Consequently, there have only been a small number of studies evaluating methods targeting hypoxia-induced radioresistance. The purpose of this systematic review is to evaluate the potential effectiveness of targeting hypoxia-induced radioresistance in rectal cancer and provide recommendations for future research in this area.<h4>Methods</h4>A comprehensive literature search was performed following the PRISMA guidelines. This study was registered on the Prospero database (CRD42023441983).<h4>Results</h4>Eight articles met the inclusion criteria. All studies identified were <i>in vitro</i> or <i>in vivo</i> studies, there were no clinical trials. Of the 8 studies identified, 5 assessed the efficacy of drugs which directly or indirectly targeted hypoxia and three that identified potential targets. There was conflicting <i>in vivo</i> evidence for the use of metformin to overcome hypoxia induced radioresistance. Vorinostat, atovaquone, and evofosfamide showed promising preclinical evidence that they can overcome hypoxia-induced radioresistance.<h4>Discussion</h4>The importance of investigating hypoxia-induced radioresistance in rectal cancer is crucial. However, to date, only a small number of preclinical studies exist evaluating this phenomenon. This systematic review highlights the importance of further research to fully understand the mechanism behind this radioresistance. There are promising targets identified in this systematic review however, substantially more pre-clinical and clinical research as a priority for future research is needed.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Hypoxia, Radiotherapy, Rectal cancer, Tumour hypoxia |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 10 Nov 2023 10:52 |
| Last Modified: | 25 Nov 2023 01:42 |
| DOI: | 10.1016/j.ctro.2023.100695 |
| Open Access URL: | https://www.ctro.science/article/S2405-6308(23)001... |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3176716 |
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