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Molecular Mechanisms Linking Exercise to Cancer Prevention and Treatment
Open accessAbstract
The benefits of exercise training for cancer patients are becoming increasingly evident. Physical exercise has been shown to reduce cancer incidence and inhibit tumor growth. Here we provide the status of the current molecular understanding of the effect of exercise on cancer. We propose that exercise has a role in controlling cancer progression through a direct effect on tumor-intrinsic factors, interplay with whole-body exercise effects, alleviation of cancer-related adverse events, and improvement of anti-cancer treatment efficacy. These findings have wide-ranging societal implications, as this understanding may lead to changes in cancer treatment strategies.
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“In addition, myokines with anticancer effects have been recognized (41, 42).”
From Muscle–Organ Crosstalk: The Emerging Roles of Myokines (2020) · cites this paper as [41]
In the citing paper
“Therefore, the anti-inflammatory effects of physical training may mediate some of the protective effects of exercise on cancer development (41).”
From Muscle–Organ Crosstalk: The Emerging Roles of Myokines (2020) · cites this paper as [41]
In the citing paper
“Epidemiological studies suggest that physical activity in leisure time reduces the risk of at least 13 different cancer types (41, 42, 222, 223).”
From Muscle–Organ Crosstalk: The Emerging Roles of Myokines (2020) · cites this paper as [41]
In the citing paper
“A few mechanistic studies have demonstrated a potential role of other myokines, including Oncostatin M, irisin, and SPARC in the suppression of breast and colon cancer growth (41, 224-227).”
From Muscle–Organ Crosstalk: The Emerging Roles of Myokines (2020) · cites this paper as [41]
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Mechanisms of exercise in the treatment of lung cancer – a mini-review
Luo, Z., Wan, R., Liu, S., Feng, X., Peng, Z., Wang, Q., Chen, S., & Shang, X. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1244764 · Cited by 35
“Exercise contributes to maintaining the balance between oxidative and antioxidative processes, lowering the risk of tumor development (60, 87).”
BackgroundRole of Regular Physical Exercise in Tumor Vasculature: Favorable Modulator of Tumor Milieu
Esteves, M., Monteiro, M. P., & Duarte, J. A. (2020) · International Journal of Sports Medicine · doi:10.1055/a-1308-3476 · Cited by 35
“Immune recognition and elimination are important intrinsic mechanisms against tumors and their immunological profile is strongly associated with cancer prognosis [242].”
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BackgroundAl-Mhanna, S. B., Ghazali, W. S. W., Mohamed, M., Rabaan, A. A., Santali, E. Y., Alestad, J. H., Santali, E., Arshad, S., Ahmed, N., & Afolabi, H. A. (2022) · PeerJ · doi:10.7717/peerj.13664 · Cited by 39
“However, human evidence is insufficient, and the clinically relevant cut-off points of the exercise-induced immuno-inflammatory response still require more investigation in cancer patients ( Pedersen et al., 2016 ; Hojman et al., 2018 ).”
Which type of exercise keeps you young?
Pedersen, B. K. (2019) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0000000000000546 · Cited by 30
Herrstedt, A., Bay, M. L., Simonsen, C., Sundberg, A., Egeland, C., Thorsen-Streit, S., Djurhuus, S. S., Ueland, P. M., Midttun, Ø., Pedersen, B. K., et al. (2019) · Acta Oncologica · doi:10.1080/0284186x.2018.1558371 · Cited by 34
“In recent years, engaging cancer patients in exercise training with the aim of controlling disease and treatment-related side effects has gained momentum, and accumulating evidence demonstrates that exercise training can lower symptoms of depression in cancer patients [4,5].”
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“In turn, physical exercise has been used as a non-pharmacological approach during cancer, regulating the symptoms of the disease, the treatment side-effects and protecting against a condition of disability or premature death [48].”
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Bouhaddou, M., Eckhardt, M., Naing, Z. Z. C., Kim, M., Ideker, T., & Krogan, N. J. (2019) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2019.04.005 · Cited by 32
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Os Benefícios dos Exercícios Físicos no Câncer de Mama
Campos, M. D. S. B., Feitosa, R. H. F., Mizzaci, C. C., von Flach, M. D. R. T., Siqueira, B. J. M., & EduardoMastrocola, L. (2022) · Arquivos Brasileiros de Cardiologia · doi:10.36660/abc.20220086 · Cited by 41
“21 Evidence that PE inhibits malignant tumor progression emerged from animal models.”
BackgroundVoluntary wheel running can lead to modulation of immune checkpoint molecule expression
Bay, M. L., Unterrainer, N., Stagaard, R., Pedersen, K. S., Schauer, T., Staffeldt, M. M., Christensen, J. F., Højman, P., Pedersen, B. K., & Gehl, J. (2020) · Acta Oncologica · doi:10.1080/0284186x.2020.1817550 · Cited by 29
Anti-carcinogenic effects of exercise-conditioned human serum: evidence, relevance and opportunities
Metcalfe, R. S., Kemp, R. N., Heffernan, S. M., Churm, R., Chen, Y., Ruffino, J. S., Conway, G. E., Tornillo, G., & Orange, S. T. (2021) · European Journal of Applied Physiology · doi:10.1007/s00421-021-04680-x · Cited by 33
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Physical exercise, health, and disease treatment: The role of macrophages
Callegari, I. O. M., Rocha, G. Z., & Oliveira, A. G. (2023) · Frontiers in Physiology · doi:10.3389/fphys.2023.1061353 · Cited by 31
“, 1999), due to which not only the immune response but also the increase in vascularization linked to the oxygen supply would contribute to antitumorigenic effects (Hojman et al., 2018).”
BackgroundAdvances in Diet and Physical Activity in Breast Cancer Prevention and Treatment
Khalifa, A., Guijarro, A. I., & Nencioni, A. (2024) · Nutrients · doi:10.3390/nu16142262 · Cited by 37
“Physical activity is also known to alleviate side effects associated with these therapies, including fatigue, nausea, and pain, thereby enhancing patients’ quality of life (QoL) [13].”
BackgroundExercise medicine in cancer care
Cormie, P., Trevaskis, M., Thornton‐Benko, E., & Zopf, E. M. (2020) · Australian Journal of General Practice · doi:10.31128/ajgp-08-19-5027 · Cited by 28
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“Exercise also supports the mechanisms of chemotherapeutic agents [20, 27].”
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“Consequently, the ability of cancer cells to form tumors in distinct tissues (Hojman et al., 2018) and the risk of developing metabolic abnormalities (Licht et al.”
BackgroundAcute exercise mobilizes CD8+ cytotoxic T cells and NK cells in lymphoma patients
Koivula, T., Lempiäinen, S., Rinne, P., Hollmén, M., Sundberg, C. J., Rundqvist, H., Minn, H. R. I., & HEINONEN, I. H. A. (2023) · Frontiers in Physiology · doi:10.3389/fphys.2022.1078512 · Cited by 27
“In preclinical studies, exercise stress has been shown to control cancer growth and metastasis as well as to improve the efficacy of cancer therapies (Pedersen et al., 2016; Hojman et al., 2018; Wennerberg et al., 2020).”
BackgroundPerego, S., Sansoni, V., Ziemann, E., & Lombardi, G. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22042005 · Cited by 29
A Single-Cell Transcriptomic Analysis of the Mouse Hippocampus After Voluntary Exercise
Methi, A., Islam, M. R., Kaurani, L., Sakib, M. S., Krüger, D. M., Pena, T., Burkhardt, S., Liebetanz, D., & Fischer, A. (2024) · Molecular Neurobiology · doi:10.1007/s12035-023-03869-9 · Cited by 33
“In addition to alleviating the risk of metabolic diseases [1–3], cardiovascular disease [1, 4, 5], and several types of cancers [6], the benefits of physical exercise on brain function have also been extensively studied and reviewed [7–10].”
The effect of diet and exercise on tobacco carcinogen-induced lung cancer
Elisia, I., Cho, B., Hay, M., Li, M. Y., Hofs, E., Lam, V., Dyer, R., Lum, J. J., & Krystal, G. (2019) · Carcinogenesis · doi:10.1093/carcin/bgz060 · Cited by 26
Cancer prevention – review paper
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“This increases the adiponectin concentration, lowering the concentration of TNF-α and IL-6 that can damage DNA, inhibit apoptosis and facilitate tumour invasion [77, 78, 79, 80].”
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Liu, H., Lu, C., Han, L., Zhang, X., & Song, G. (2021) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2021.213978 · Cited by 26
Exercise oncology: an emerging discipline in the cancer care continuum
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“growth and progression via hemodynamic (vasoconstriction and increased blood flow) and hormonal mechanisms (decrease in stress hormone levels) [30].”
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“, C-reactive protein, adiponectin and interleukin-6) [34, 47, 48], which are associated with a higher risk of cancer [49, 50].”
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“Whether prolonged exercise combined with severe energy deficit could elicit FoxOs downregulation in cancer cells remains unknown, but this may be another mechanism by which exercise could have beneficial effects in some cancers [52].”
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DiJoseph, K., Thorp, A., Harrington, A., Schmitz, K. H., Chinchilli, V. M., & Stine, J. G. (2023) · Digestive Diseases and Sciences · doi:10.1007/s10620-022-07601-w · Cited by 25
The Effects of Physical Exercise on Tumor Vasculature: Systematic Review and Meta-analysis
Esteves, M., Monteiro, M. P., & Duarte, J. A. (2021) · International Journal of Sports Medicine · doi:10.1055/a-1533-1876 · Cited by 26
Lee, M., Lee, Y., Jang, D., & Shin, A. (2021) · Cancers · doi:10.3390/cancers13194804 · Cited by 27
Association of Physical Activity and Sedentary Behavior With the Risk of Colorectal Cancer
An, S., & Park, S. (2022) · Journal of Korean Medical Science · doi:10.3346/jkms.2022.37.e158 · Cited by 25
The effects of acute exercise and inflammation on immune function in early-stage prostate cancer
Schauer, T., Djurhuus, S. S., Simonsen, C., Brasso, K., & Christensen, J. F. (2022) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2022.100508 · Cited by 25
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Exercise and health: historical perspectives and new insights
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Papadopoulos, E., Gillen, J. B., Moore, D., Au, D., Kurgan, N., Klentrou, P., Finelli, A., Alibhai, S. M. H., & Mina, D. S. (2021) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/apnm-2021-0365 · Cited by 25
Santi, M. D., Baldelli, G., Lucertini, F., Natalucci, V., Brandi, G., & Barbieri, E. (2019) · Data in Brief · doi:10.1016/j.dib.2019.104704 · Cited by 24
“This Data in Brief presents the optimization of methods for the evaluation of triple negative breast cancer (TNBC) [1,2] cell MDA-MB-231 responses induced by acute exercise-conditioned sera [3,4], considering also the capacity of exercise-conditioned sera to modulate three-dimensional (3D) anchorage-independent cancer…”
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“Exercise regulates the levels of numerous hormones in the body, with adrenaline being one of the most frequently affected hormones [19].”
BackgroundChronic stress: a fourth etiology in tumorigenesis?
Khan, A., Song, M., & Dong, Z. (2025) · Molecular Cancer · doi:10.1186/s12943-025-02402-x · Cited by 30
“However, epinephrine is also shown to decrease tumor burden by activating NK cell mobilization and redistribution [142, 143].”
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“Recent evidence points to a number of effects of exercise that lead to tumor growth inhibition, as reviewed previously (Hojman et al., 2018), and the current paper adds to the list of factors that may explain the rather striking findings placing exercise as central in cancer prevention.”
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“Physical activity has been associated with a reduced risk of developing many cancers including cancer of the breast [2–6], but the exact biological mechanisms are not completely understood [7,8].”
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Embedded of Nanogel into Multi-responsive Hydrogel Nanocomposite for Anticancer Drug Delivery
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Lognos, B., Carbonnel, F., Boulze-Launay, I., Bringay, S., Guerdoux, E., Mollévi, C., Sénesse, P., & Ninot, G. (2019) · JMIR Cancer · doi:10.2196/12536 · Cited by 23
“The physical activity subcategory is predominant and is consistent with recent mechanistic studies [29,30], meta-analyses [31,32], and authorities’ recommendations [33,34].”
ResultOrlandella, F. M., Stefano, A. E. D., Iervolino, P. L. C., Buono, P., Soricelli, A., & Salvatore, G. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.118790 · Cited by 23
Djurhuus, S. S., Schauer, T., Simonsen, C., Toft, B. G., Jensen, A. R. D., Erler, J. T., Røder, M. A., Højman, P., Brasso, K., & Christensen, J. F. (2022) · Physiological Reports · doi:10.14814/phy2.15408 · Cited by 22
“As vessel diameter is the dominant parameter in flow regulation (Hojman et al., 2018), it could be speculated that the increased systemic blood flow and MAP during exercise, together with the reduced myogenic constriction of the tumor vessels in response to norepinephrine, may increase tumor vessel diameter resulting…”
BackgroundWen, L., Chen, X., Cui, Y., Zhang, M., & Bai, X. (2022) · Supportive Care in Cancer · doi:10.1007/s00520-022-07548-8 · Cited by 23
“Existing studies have shown that exercise can have direct anticancer effects by influencing intrinsic tumour factors, thereby playing an important role in the control of cancer progression; thus, it is recommended that exercise training should be incorporated into the standard treatment of cancer patients [8].”
BackgroundFarley, M. J., Bartlett, D. B., Skinner, T. L., Schaumberg, M. A., & Jenkins, D. G. (2022) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000003067 · Cited by 24
“Copyright © 2023 by the American College of Sports Medicine treatment efficacy, completion rates, and subsequent patient outcomes (5).”
BackgroundUnveiling the Intricate Dance: How Cancer Orchestrates Muscle Wasting and Sarcopenia
Lavalle, S., Valerio, M. R., Masiello, E., Gebbia, V., & Scandurra, G. (2024) · In Vivo · doi:10.21873/invivo.13602 · Cited by 23
“These effects include enhanced blood circulation, activation of the sympathetic nervous system, regulation of hormone levels, and mobilization of cytotoxic lymphocytes and natural killer (NK) cells, resulting in a potential antitumor effect through these mechanisms (79).”
BackgroundExercise and Oxidative Stress Biomarkers among Adult with Cancer: A Systematic Review
Longobucco, Y., Masini, A., Marini, S., Barone, G., Fimognari, C., Bragonzoni, L., Dallolio, L., & Maffei, F. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/2097318 · Cited by 27
“In people with cancer, exercise is linked to positive mod-i fi cations in cardiorespiratory fi tness, physical function, and in anthropometric composition, as well as in patient-reported health bene fi t in quality of life and manage of fatigue [9 – 11].”
Kayacan, Y., Çetinkaya, A., Yazar, H., & Makaracı, Y. (2019) · Archives of Physiology and Biochemistry · doi:10.1080/13813455.2019.1651868 · Cited by 21
“Regular physical exercise is effective in reducing the threat of mortality due to cardiovascular diseases (Kayacan and Yildiz 2016), cancer (Hojman et al. 2018), diabetes and all other causes (Melmer et al. 2018).”
BackgroundHardee, J. P., Fix, D. K., Koh, H., Wang, X., Goldsmith, E. C., & Carson, J. A. (2020) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00908.2019 · Cited by 21
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“Engaging in regular PA optimizes health outcomes (Rock et al. 2022), treatment effectiveness (Hojman et al. 2018), tolerance (Hojman et al. 2018), and quality of life (QoL) (Liska and Kolen 2020), while also reducing the risk of mortality and recurrence in cancer survivors (Morishita et al. 2020).”
BackgroundFilis, P., Markozannes, G., Chan, D. S. M., Mauri, D., Foukakis, T., Matikas, A., Droufakou, S., Pentheroudakis, G. E., & Tsilidis, K. K. (2024) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2024.104602 · Cited by 27
Mlynska, A., Dobrovolskienė, N., Žilionytė, K., Lukaseviciute, G., Sagini, K., Martin-Gracia, B., Romero, S., Llorente, A., Linē, A., Butkute, A., et al. (2025) · Journal of sport and health science/Journal of Sport and Health Science · doi:10.1016/j.jshs.2025.101041 · Cited by 20
Vainshelboim, B., Chen, Z., Lima, R. M., & MYERS, J. N. (2019) · Journal of Physical Activity and Health · doi:10.1123/jpah.2019-0245 · Cited by 20
Exercise training as prophylactic strategy in the management of neutropenia during chemotherapy
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“type-2 diabetes, and cardiovascular disease, as well as cancer [17,51].”
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“56 Another limitation lies in our analysis of the isolated mitochondrial morphology of CD8 + TILs, as the T cell purification process from digested tumors could potentially induce significant changes in mitochondrial dynamics and function.”
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“PA has attracted much attention as a potential protective factor against cancer-related deaths, recurrence, or metastasis (4-6 , 36).”
Role and mechanisms of exercise therapy in enhancing drug treatment for glioma: a review
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“While published murine model studies have demonstrated a reduction in tumor growth through aerobic exercise training (18, 19), only a limited few have investigated the combination of exercise with immune-chemotherapeutic treatments and no study has evaluated the effect of exercise immediately…”
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“This adaptation to ROS may lower the risk of ROS-related diseases through exercise, including some cardiovascular diseases, stroke, Alzheimer’s disease, and certain cancers [118,119].”
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“Hence, physical activity and supplement substances with anticancer medications have been shown to augment therapeutic effectiveness and mitigate the systemic toxicity associated with chemotherapy medicines [24].”
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Metadata
- Authors
- Hojman, P., Gehl, J., Christensen, J. F., & Pedersen, B. K.
- Affiliations
- Herlev Hospital (DK)
- University of Copenhagen (DK)
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2018-01
- Volume
- 27
- Issue
- 1
- Pages
- 10-21
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2765400080
- Cited by
- 600
- References
- 112
- Citations by year
- 2026: 63 · 2025: 78 · 2024: 86 · 2023: 71 · 2022: 90 · 2021: 77 · 2020: 70 · 2019: 38 · 2018: 25
- FWCI
- 3.43
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Danmarks Grundforskningsfond (DNRF55)
- Strategiske Forskningsråd (09-067009, 09-075724)
- TrygFonden
- Kræftens Bekæmpelse
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Physiology (medical) › Exercise and Physiological Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Keywords
- physical activity, cancer prevention, cancer therapy, tumor growth inhibition, tumor progression, tumor-intrinsic factors, exercise-induced metabolic changes, molecular mechanisms
- MeSH terms
- Humans, Immunity, Models, Biological, Neoplasms, Exercise, Carcinogenesis
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