Modulating Tumour Hypoxia in Prostate Cancer Through Exercise: The Impact of Redox Signalling on Radiosensitivity

Brown, Malcolm; Rébillard, Amélie; Hart, Nicolas H.; O’Connor, Dominic; Prue, Gillian; O’Sullivan, Joe M.; Jain, Suneil

Abstract

Prostate cancer is a complex disease affecting millions of men globally. Radiotherapy (RT) is a common treatment modality although treatment efficacy is dependent upon several features within the tumour microenvironment (TME), especially hypoxia. A hypoxic TME heightens radioresistance and thus disease recurrence and treatment failure continues to pose important challenges. However, the TME evolves under the influence of factors in systemic circulation and cellular crosstalk, underscoring its potential to be acutely and therapeutically modified. Early preclinical evidence suggests exercise may affect tumour growth and some of the benefits drawn, could act to radiosensitise tumours to treatment. Intracellular perturbations in skeletal muscle reactive oxygen species (ROS) stimulate the production of numerous factors that can exert autocrine, paracrine, and endocrine effects on the prostate. However, findings supporting this notion are limited and the associated mechanisms are poorly understood. In light of this preclinical evidence, we propose systemic changes in redox signalling with exercise activate redox-sensitive factors within the TME and improve tumour hypoxia and treatment outcomes, when combined with RT. To this end, we suggest a connection between exercise, ROS and tumour growth kinetics, highlighting the potential of exercise to sensitise tumour cells to RT, and improve treatment efficacy.

Citation

Brown, M., Rébillard, A., Hart, N. H., O’Connor, D., Prue, G., O’Sullivan, J. M., & Jain, S. (2022). Modulating Tumour Hypoxia in Prostate Cancer Through Exercise: The Impact of Redox Signalling on Radiosensitivity. Sports Medicine - Open, 8(1), https://doi.org/10.1186/s40798-022-00436-9

• Journal Article Type: Article
• Acceptance Date: Mar 20, 2022
• Online Publication Date: Apr 8, 2022
• Publication Date: Apr 8, 2022
• Deposit Date: Oct 2, 2023
• Publicly Available Date: Oct 3, 2023
• Journal: Sports Medicine - Open
• Print ISSN: 2199-1170
• Electronic ISSN: 2198-9761
• Publisher: Springer Verlag
• Peer Reviewed: Peer Reviewed
• Volume: 8
• Issue: 1
• DOI: https://doi.org/10.1186/s40798-022-00436-9
• Keywords: Physical Therapy, Sports Therapy and Rehabilitation; Orthopedics and Sports Medicine
• Public URL: https://nottingham-repository.worktribe.com/output/12036455
• Publisher URL: https://sportsmedicine-open.springeropen.com/articles/10.1186/s40798-022-00436-9
• Additional Information: Received: 21 July 2021; Accepted: 20 March 2022; First Online: 8 April 2022; : ; : Not applicable.; : Not applicable.; : Malcolm Brown, Amélie Rébillard, Nicolas Hart, Dominic O’Connor, Gillian Prue, Joe O’Sullivan and Suneil Jain declare that they have no conflicts of interest relevant to the content of this article.