Exercise modulation of tumour perfusion and hypoxia to improve radiotherapy response in prostate cancer

Abstract

Background An increasing number of studies indicate that exercise plays an important role in the overall care of prostate cancer (PCa) patients before, during and after treatment. Historically, research has focused on exercise as a modulator of physical function, psychosocial well-being as well as a countermeasure to cancer-and treatment-related adverse effects. However, recent studies reveal that exercise may also directly influence tumour physiology that could beneficially affect the response to radiotherapy. Methods In this narrative review, we provide an overview of tumour vascular characteristics that limit the effect of radiation and establish a rationale for exercise as adjunct therapy during PCa radiotherapy. Further, we summarise the existing literature on exercise as a modulator of tumour perfusion and hypoxia and outline potential future research directions. Results Preclinical research has shown that exercise can reduce intratumoral hypoxia-a major limiting factor in radiotherapy-by improving tumour perfusion and vascularisation. In addition, preliminary evidence suggests that exercise training can improve radiotherapy treatment outcomes by increasing natural killer cell infiltration in a murine PCa model. Conclusions Exercise is a potentially promising adjunct therapy for men with PCa undergoing radiotherapy that may increase its effectiveness. However, exercise-induced tumour radiosensitisation remains to be confirmed in preclinical and clinical trials, as does the optimal exercise prescription to elicit such effects.

Effects of Exercise During Radiation Therapy on Physical Function and Treatment-Related Side Effects in Men With Prostate Cancer: A Systematic Review and Meta-Analysis

“…during vs. after radiotherapy) or different exercise prescriptions (e.g. comparing different exercise modalities and intensities) may affect treatment toxicity including assessment of long-term follow-up of side effects as well as potential mechanisms of action for exercise as an adjunct therapy during radiotherapy in patients with prostate cancer [63]. with the assessment timepoints for the longest duration of radiotherapy reported).…”

Anti-carcinogenic effects of exercise-conditioned human serum: evidence, relevance and opportunities

“…hormones) require transport via receptor-mediated or other transcellular pathways (Mehta and Malik 2006). At the same time, tumour vascular networks are heterogeneous, and often immature and dysfunctional, leading to highly variable tumour blood flow and perfusion across whole tumours, or within different regions within a single tumour (Chung et al 2010;Hughes et al 2019;Schumacher et al 2020). Poor perfusion of the tumour microenvironment can have a direct impact on the delivery of nutrients [e.g.…”

The Effects of Physical Exercise on Tumor Vasculature: Systematic Review and Meta-analysis

“…Therefore, while angiogenesis-inhibiting agents commonly used in oncology therapies such as Bevacizumab act by blocking the angiogenic stimuli in order to inhibit new vessel formation, physical exercise does not seem to involve tumor vessel pruning but instead, by inducing significant vascular maturation, it renders the vessels more stable [9]. As a result, considering that vessel leakiness is associated with tumor progression and dissemination, the blood vessel modulation induced by physical exercise seems to make the tumor vasculature more functional, increasing tumor perfusion and inhibiting its proliferation potential [57].…”