Brown Malcolm, Rébillard Amélie, Hart Nicolas H, O'Connor Dominic, Prue Gillian, O'Sullivan Joe M, Jain Suneil
School of Nursing and Midwifery, Queen's University Belfast, Northern Ireland, Belfast, UK.
Movement, Sport and Health Sciences Laboratory, Université Rennes 2, ENS Rennes, Bruz, France.
Sports Med Open. 2022 Apr 8;8(1):48. doi: 10.1186/s40798-022-00436-9.
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.
前列腺癌是一种复杂的疾病，全球数百万男性受其影响。放射治疗（RT）是一种常见的治疗方式，尽管治疗效果取决于肿瘤微环境（TME）中的几个特征，尤其是缺氧情况。缺氧的肿瘤微环境会增强放射抗性，因此疾病复发和治疗失败仍然是重大挑战。然而，肿瘤微环境在全身循环因素和细胞间相互作用的影响下会发生演变，这突出了其进行急性和治疗性改变的潜力。早期临床前证据表明，运动可能会影响肿瘤生长，并且由此带来的一些益处可能会使肿瘤对治疗产生放射增敏作用。骨骼肌活性氧（ROS）的细胞内扰动会刺激多种因子的产生，这些因子可对前列腺产生自分泌、旁分泌和内分泌作用。然而，支持这一观点的研究结果有限，相关机制也知之甚少。鉴于这一临床前证据，我们提出运动引起的氧化还原信号的全身变化会激活肿瘤微环境中的氧化还原敏感因子，并在与放射治疗联合使用时改善肿瘤缺氧情况和治疗效果。为此，我们提出运动、ROS与肿瘤生长动力学之间的联系，强调运动使肿瘤细胞对放射治疗敏感并提高治疗效果的潜力。
