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      Cancer and Exercise: Warburg Hypothesis, Tumour Metabolism and High-Intensity Anaerobic Exercise

      review-article
      Sports
      MDPI
      high-intensity exercise, cancer metabolism, lactate, inhibition, exercise prescription

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          Abstract

          There is ample evidence that regular moderate to vigorous aerobic physical activity is related to a reduced risk for various forms of cancer to suggest a causal relationship. Exercise is associated with positive changes in fitness, body composition, and physical functioning as well as in patient-reported outcomes such as fatigue, sleep quality, or health-related quality of life. Emerging evidence indicates that exercise may also be directly linked to the control of tumour biology through direct effects on tumour-intrinsic factors. Beside a multitude of effects of exercise on the human body, one underscored effect of exercise training is to target the specific metabolism of tumour cells, namely the Warburg-type highly glycolytic metabolism. Tumour metabolism as well as the tumour–host interaction may be selectively influenced by single bouts as well as regularly applied exercise, dependent on exercise intensity, duration, frequency and mode. High-intensity anaerobic exercise was shown to inhibit glycolysis and some studies in animals showed that effects on tumour growth might be stronger compared with moderate-intensity aerobic exercise. High-intensity exercise was shown to be safe in patients; however, it has to be applied carefully with an individualized prescription of exercise.

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          Most cited references93

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          On the origin of cancer cells.

          O WARBURG (1956)
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            Lactate: a metabolic key player in cancer.

            Increased glucose uptake and accumulation of lactate, even under normoxic conditions (i.e., aerobic glycolysis or the Warburg Effect), is a common feature of cancer cells. This phenomenon clearly indicates that lactate is not a surrogate of tumor hypoxia. Tumor lactate can predict for metastases and overall survival of patients, as shown by several studies of different entities. Metastasis of tumors is promoted by lactate-induced secretion of hyaluronan by tumor-associated fibroblasts that create a milieu favorable for migration. Lactate itself has been found to induce the migration of cells and cell clusters. Furthermore, radioresistance has been positively correlated with lactate concentrations, suggesting an antioxidative capacity of lactate. Findings on interactions of tumor metabolites with immune cells indicate a contribution of lactate to the immune escape. Furthermore, lactate bridges the gap between high lactate levels in wound healing, chronic inflammation, and cancer development. Tumor cells ensure sufficient oxygen and nutrient supply for proliferation through lactate-induced secretion of VEGF, resulting in the formation of new vessels. In summary, accumulation of lactate in solid tumors is a pivotal and early event in the development of malignancies. The determination of lactate should enter further clinical trials to confirm its relevance in cancer biology. ©2011 AACR
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              Cancer's molecular sweet tooth and the Warburg effect.

              More than 80 years ago, the renowned biochemist Otto Warburg described how cancer cells avidly consume glucose and produce lactic acid under aerobic conditions. Recent studies arguing that cancer cells benefit from this phenomenon, termed the Warburg effect, have renewed discussions about its exact role as cause, correlate, or facilitator of cancer. Molecular advances in this area may reveal tactics to exploit the cancer cell's "sweet tooth" for cancer therapy.
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                Author and article information

                Journal
                Sports (Basel)
                Sports (Basel)
                sports
                Sports
                MDPI
                2075-4663
                31 January 2018
                March 2018
                : 6
                : 1
                : 10
                Affiliations
                Institute of Sports Sciences, Exercise Physiology, Training & Training Therapy Research Group, University of Graz, Max Mell Allee 11, Graz 8010, Austria; peter.hofmann@ 123456uni-graz.at ; Tel.: +43-316-380-3903
                Author information
                https://orcid.org/0000-0003-4836-1238
                Article
                sports-06-00010
                10.3390/sports6010010
                5969185
                29910314
                426674c5-b449-4eb6-a176-6f72cb437823
                © 2018 by the author.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 02 November 2017
                : 29 January 2018
                Categories
                Review

                high-intensity exercise,cancer metabolism,lactate,inhibition,exercise prescription

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