Enhancing radiotherapy outcomes in rectal cancer: A systematic review of targeting hypoxia-induced radioresistance
Introduction: 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...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-01-01
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| Series: | Clinical and Translational Radiation Oncology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405630823001209 |
| _version_ | 1797398540753829888 |
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| author | Matthew Fok Rhianna Hill Hayley Fowler Rachael Clifford Aaron Kler Jayanma Uzzi-Daniel Sonia Rocha Gabrielle Grundy Jason Parsons Dale Vimalachandran |
| author_facet | Matthew Fok Rhianna Hill Hayley Fowler Rachael Clifford Aaron Kler Jayanma Uzzi-Daniel Sonia Rocha Gabrielle Grundy Jason Parsons Dale Vimalachandran |
| author_sort | Matthew Fok |
| collection | DOAJ |
| description | Introduction: 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. Methods: A comprehensive literature search was performed following the PRISMA guidelines. This study was registered on the Prospero database (CRD42023441983). Results: Eight articles met the inclusion criteria. All studies identified were in vitro or in vivo 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 in vivo 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. Discussion: 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. |
| first_indexed | 2024-03-09T01:26:58Z |
| format | Article |
| id | doaj.art-05c15f1c8f4a4c4186458900566e0667 |
| institution | Directory Open Access Journal |
| issn | 2405-6308 |
| language | English |
| last_indexed | 2024-03-09T01:26:58Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Clinical and Translational Radiation Oncology |
| spelling | doaj.art-05c15f1c8f4a4c4186458900566e06672023-12-10T06:16:36ZengElsevierClinical and Translational Radiation Oncology2405-63082024-01-0144100695Enhancing radiotherapy outcomes in rectal cancer: A systematic review of targeting hypoxia-induced radioresistanceMatthew Fok0Rhianna Hill1Hayley Fowler2Rachael Clifford3Aaron Kler4Jayanma Uzzi-Daniel5Sonia Rocha6Gabrielle Grundy7Jason Parsons8Dale Vimalachandran9Institute of Systems, Molecular and Integrative Biology University of Liverpool, UK; Corresponding author at: Institute of Systems, Molecular and Integrative Biology, University of Liverpool, William Henry Duncan Building, L7 8TX, UK.Institute of Systems, Molecular and Integrative Biology University of Liverpool, UKInstitute of Systems, Molecular and Integrative Biology University of Liverpool, UKInstitute of Systems, Molecular and Integrative Biology University of Liverpool, UKInstitute of Systems, Molecular and Integrative Biology University of Liverpool, UKInstitute of Systems, Molecular and Integrative Biology University of Liverpool, UKInstitute of Systems, Molecular and Integrative Biology University of Liverpool, UKInstitute of Systems, Molecular and Integrative Biology University of Liverpool, UKInstitute of Cancer and Genomic Sciences, University of Birmingham, UKInstitute of Systems, Molecular and Integrative Biology University of Liverpool, UK; Countess of Chester Hospital, Colorectal Surgery Department, Chester, UKIntroduction: 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. Methods: A comprehensive literature search was performed following the PRISMA guidelines. This study was registered on the Prospero database (CRD42023441983). Results: Eight articles met the inclusion criteria. All studies identified were in vitro or in vivo 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 in vivo 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. Discussion: 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.http://www.sciencedirect.com/science/article/pii/S2405630823001209Rectal cancerTumour hypoxiaRadiotherapyHypoxia |
| spellingShingle | Matthew Fok Rhianna Hill Hayley Fowler Rachael Clifford Aaron Kler Jayanma Uzzi-Daniel Sonia Rocha Gabrielle Grundy Jason Parsons Dale Vimalachandran Enhancing radiotherapy outcomes in rectal cancer: A systematic review of targeting hypoxia-induced radioresistance Clinical and Translational Radiation Oncology Rectal cancer Tumour hypoxia Radiotherapy Hypoxia |
| title | Enhancing radiotherapy outcomes in rectal cancer: A systematic review of targeting hypoxia-induced radioresistance |
| title_full | Enhancing radiotherapy outcomes in rectal cancer: A systematic review of targeting hypoxia-induced radioresistance |
| title_fullStr | Enhancing radiotherapy outcomes in rectal cancer: A systematic review of targeting hypoxia-induced radioresistance |
| title_full_unstemmed | Enhancing radiotherapy outcomes in rectal cancer: A systematic review of targeting hypoxia-induced radioresistance |
| title_short | Enhancing radiotherapy outcomes in rectal cancer: A systematic review of targeting hypoxia-induced radioresistance |
| title_sort | enhancing radiotherapy outcomes in rectal cancer a systematic review of targeting hypoxia induced radioresistance |
| topic | Rectal cancer Tumour hypoxia Radiotherapy Hypoxia |
| url | http://www.sciencedirect.com/science/article/pii/S2405630823001209 |
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