Exercise to combat cancer: focusing on the ends.

Abstract

Cancer remains a leading cause of death worldwide and although prognosis and survivorship after therapy has improved significantly, current cancer treatments have long-term health consequences. For decades telomerase-mediated telomere maintenance has been an attractive anti-cancer therapeutic target due to its abundance and role in telomere maintenance, pathogenesis and growth in neoplasms. Telomere maintenance-specific cancer therapies, however, are marred by off target side-effects that must be addressed before they reach clinical practice. Regular exercise training is associated with telomerase-mediated telomere maintenance in healthy cells, which is associated with healthy ageing. A single bout of endurance exercise training dynamically, but temporarily, increases TERT mRNA and telomerase activity, as well as several molecules that control genomic stability and telomere length (i.e., shelterin and TERRA). Considering the epidemiological findings and accumulating research highlighting that exercise significantly reduces the risk of many types of cancers and the anti-carcinogenic effects of exercise on tumour growth in vitro, investigating the governing molecular mechanisms of telomerase control in context with exercise and cancer may provide important new insights to explain these findings. Specifically, the molecular mechanisms controlling telomerase in both healthy cells and tumours after exercise could reveal novel therapeutic targets for tumour-specific telomere maintenance and offer important evidence that could refine current physical activity and exercise guidelines for all stages of cancer care.