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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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“7,8 10 In conjunction with the health benefits, exercise and rehabilitation services can provide an improvement in quality of life through services such as physiatry; physical, occupational, and speech therapy; and psychotherapy.”
BackgroundAn online home-based exercise program improves autonomic dysfunction in breast cancer survivors
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Chen, H., Zhou, H., Wu, B., Lu, H., Zhang, J., Zhang, Y., Gu, Y., Guangwen, Z., Xiang, J., & Yang, J. (2024) · Liver Research · doi:10.1016/j.livres.2024.03.001 · Cited by 5
“Furthermore, aside from the general health bene fi ts, existing research suggests that exercise training has cancer-speci fi c bene fi ts. 32 e 37 While bene fi cial, antitumor treatments can cause fatigue, depression, anxiety, and lymphedema.”
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“These biological adap-tions may influence cancer progression through direct effect on tumor intrinsic factors (e.g., growth rate and metastasis) and growth through an interplay with systemic factors [3, 4], which may ultimately improve cancer survivorship.”
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“PA can positively influence systemic functions such as insulin metabolism, immune response, and inflammation, which are believed to help reduce cancer risk [18, 21, 22].”
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“Long-term physical training adapts the tumour microenvironment by activating AMPK and inhibiting PI3K–AKT–mTOR signalling 3 .”
Kim, Y. W., Kwak, K. I., Choi, A., Park, E. J., Lee, B. J., Lee, Y. J., & Lee, C. (2025) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.70092 · Cited by 3
“The potential protective biological mechanisms of PA against cancer include modulation of oncogenic factors such as insulin-like growth factors and inflammatory cytokines, as well as improvement in immunogenicity and metabolic function [14, 40].”
Stubbins, R., Li, B., Vasquez, M., Gorman, B. K., Zambelas, J. M., Allenson, K., Dhala, A. F., Dong, W., Zhao, H., & Wong, S. T. C. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27020943 · Cited by 3
Zhang, Y., Zhang, Y., Shen, C., Li, J., Wang, H., Hamad, A. B., Cao, C., Moheb, M. E., Wang, Y., Xia, Y., et al. (2026) · Cell Reports Medicine · doi:10.1016/j.xcrm.2026.102589 · Cited by 3
Chronic exercise training intensity, immune cells, and cancer outcomes: a scoping review
Kang, D.-W., Courneya, K. S., Swartz, M. C., Vareki, S. M., Gordon, N. B., Neto, J. C. R., Simpson, R. J., Baker, K. S., Schadler, K., & LaVoy, E. C. P. (2026) · JNCI Cancer Spectrum · doi:10.1093/jncics/pkag021 · Cited by 3
“52,53 The immune challenge differs between cancer types and thus the desired response to exercise differs in each scenario.”
Mănescu, D. C., Plastoi, C. D., Pîrvan, A., Dîrnu, R., Floroiu, E. A., & Popescu, A. (2026) · Cells · doi:10.3390/cells15141236 · Cited by 5
“The disease-specific remodeling patterns summarized in [20,93,94,107–110] Muscle loss, fatigue and reduced treatment tolerance Exercise oncology requiresdisease-specific prescription [109,110] Note.”
Esteves, M., Silva, C., Bovolini, A., Pereira, S. S., Morais, T., Moreira, Â., Costa, M. M., Monteiro, M. P., & Duarte, J. A. (2023) · International Journal of Sports Medicine · doi:10.1055/a-2008-7732 · Cited by 3
“Indeed, current evidence indicates that moderate to high-intensity endurance exercise is superior to light exercise, when aiming to target tumor intrinsic factors [74].”
BackgroundGonzález-Santos, Á., López-Garzón, M., Gil-Gutiérrez, R., Salinas-Asensio, M. M., Postigo-Martin, P., & Cantarero-Villanueva, I. (2023) · Physical Therapy · doi:10.1093/ptj/pzad070 · Cited by 3
“25 Many direct and indirect anticancer mechanisms of action have been described, and they are clearly interrelated, especially the inflammation, immunity, and insulin resistance pathways.”
Fukushima, T., Katsushima, U., Ogushi, N., Hase, K., & Nakano, J. (2024) · BMJ Supportive & Palliative Care · doi:10.1136/spcare-2024-005122 · Cited by 3
Jamrasi, P., Tazi, M., Zulkifli, N. A. B., Bae, J. H., & Song, W. J. (2024) · The Journal of Physiological Sciences · doi:10.1186/s12576-024-00950-3 · Cited by 3
“The effect of physical activity has shown promise on the following outcomes: efficacy of such as reduction of some symptoms of cancer [79], palliative care on quality of life [80], and reduction of the side effects of cancer treatments [14].”
InfluentialJiang, Z., Wang, B., Zhao, Y., Weng, J., Sun, K., Zhao, Z., Luo, R., Zhang, Z., Zhou, X., Zhang, Z., et al. (2025) · The journal of nutrition health & aging · doi:10.1016/j.jnha.2025.100586 · Cited by 3
RETRACTED: Physical activity and glioblastoma: a paradigm shift in neuro-oncology therapy
Xie, L., & Wang, F. (2025) · Frontiers in Oncology · doi:10.3389/fonc.2025.1638060 · Cited by 5
“It is well established that elevated lactate levels in the TME stimulate angiogenesis and may inhibit cytotoxic immunological T cell function (207).”
RetractedChulvi‐Medrano, I., Rebullido, T. R., Gómez‐Tomás, C., & Faigenbaum, A. D. (2020) · Journal of Bodywork and Movement Therapies · doi:10.1016/j.jbmt.2020.02.019 · Cited by 3
Merellano-Navarro, E., Olate‐Briones, A., Norambuena-Mardones, L., Rojas-Ramos, V., de la Plata-Luna, A. M., Faúndez-Acuña, J. Y., Moraga, J. C., Escobedo, N., & Herrada, A. A. (2021) · International Journal of Morphology · doi:10.4067/s0717-95022021000300789 · Cited by 3
Antoni, M. F., Rejeki, P. S., Sulistiawati, S., Pranoto, A., & Sugiharto, D. (2022) · International Journal of Research Publications · doi:10.47119/ijrp100931120222779 · Cited by 3
Fu, J. C., Fu, P., & Cheng, Y. (2022) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph192416773 · Cited by 3
LncRNA FTH1P3: A New Biomarker for Cancer-Related Therapeutic Development
Darvish, M. (2023) · Current Molecular Medicine · doi:10.2174/1566524023666230724141353 · Cited by 3
Peinado, B. R. R., Frazão, D. R., Chemelo, V. S., Matos‐Sousa, J. M., Ferreira, R. D. O., Bittencourt, L. O., Balbinot, G. D. S., Collares, F. M., Fernandes, L. M. P., Maia, C. D. S. F., et al. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.116554 · Cited by 3
“The 2020 WHO guideline recommends at least 150 – 300 min of moderate-intensity physical activity per week [47,48,62].”
Effects of exercise training on prostate cancer: Current evidence and potential molecular mechanisms
Webber, M., Li, M., Cai, C., & Zou, K. (2024) · Advanced Exercise and Health Science · doi:10.1016/j.aehs.2024.08.003 · Cited by 3
Wang, Y., Qin, Y., Xu, X., Li, Y., Zhu, X. L., Yang, G., XU, Y., Yao, F., & Guo, G. (2024) · BMJ Open · doi:10.1136/bmjopen-2024-092363 · Cited by 3
“15 However, at present, there is still a lack of evidence that PCa patients undergoing ADT can use moderate-intensity exercise prescriptions.”
Tichy, L., & Parry, T. L. (2024) · JCSM Communications · doi:10.1002/rco2.103 · Cited by 3
“Previous studies of moderate to high-intensity exercise protocols have shown that mice experienced decreased tumour growth, based on tumour mass and volume, by − 20% to − 67% compared with sedentary counter-parts [11, 34, 35].”
Tichy, L., Allred, K. F., Rezeli, E. T., Coleman, M. F., Allred, C. D., Hursting, S. D., & Parry, T. L. (2025) · Cells · doi:10.3390/cells14120924 · Cited by 3
“While the anti-inflammatory and anabolic effects of exercise are well described in the literature [38,39], the effects of exercise and physical activity on Atrogin1 and MuRF1 expression and cancer-mediated cardiac cachexia remain unknown.”
Exercise Oncology from Diagnosis to Treatment: An Overview of Outcomes and Considerations
Fairman, C. M., & Galvao, D. A. (2020) · Springer eBooks · doi:10.1007/978-3-030-42011-6_5 · Cited by 3
Parra, M. T., Esmeaeli, N., Kohn, J. N., Henry, B. L., Klagholz, S. D., Jain, S., Pruitt, C., Vicario, D., Jonas, W. B., & Mills, P. J. (2020) · Integrative Cancer Therapies · doi:10.1177/1534735420921439 · Cited by 3
Bovolini, A., Garcia, J., Andrade, M. A., & Duarte, J. A. (2020) · Physiology & Behavior · doi:10.1016/j.physbeh.2020.113040 · Cited by 5
Aponte-Serrano, J. O., & Hagar, A. (2021) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-020-02790-7 · Cited by 3
Regulation of the Effect of Physical Activity Through MicroRNAs in Breast Cancer
Hong, B. S. (2021) · International Journal of Sports Medicine · doi:10.1055/a-1678-7147 · Cited by 3
Darragh, I. A. J., Martinez‐Pacheco, S., O’Driscoll, L., & Egan, B. (2023) · Experimental Physiology · doi:10.1113/ep091383 · Cited by 3
“…alterations to tumour metabolism induced by acute exercise, and enhanced immune cell recognition of tumour cells, both of which may be caused by an exercise-induced increase in circulating ‘exercise factors’ (e.g., Interleukin-6) (Hojman et al., 2018; Metcalfe et al., 2021; Pedersen et al., 2016).”
BackgroundObi, P. O., de Souza, T. D. F. G., McManus, K. J., West, A. R., Gordon, J. W., & Saleem, A. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.08.29.610232 · Cited by 3
Mateluna, C., Romualdo Ibáñez, O., Campos-Rojas, C., Covarrubias, A. S., Figueroa, R. F., & Martínez‐Flores, R. (2025) · Behavioral Sciences · doi:10.3390/bs15010077 · Cited by 2
Bos, M. D., Sidorenkov, G. A., Vinke, P. C., Ho, C. S. L., Meyer, N. H., Bockhorn, M., de Groot, D. J., Klaase, J. M., Hoogwater, F. J. H., de Bock, G. H., et al. (2025) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-25-0608 · Cited by 2
“From a biological perspective, physical activity may reduce tumor growth and metastatic spread by directly influencing the tumor microenvironment through the modulation of tumor metabolism, angiogenesis, and the local immune response (9–12).”
Roles of long non-coding RNA HULC in human digestive system cancers
Huang, L. (2025) · Frontiers in Oncology · doi:10.3389/fonc.2025.1642425 · Cited by 2
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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