{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T18:55:11Z","timestamp":1789152911194,"version":"build-2803163510"},"reference-count":377,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T00:00:00Z","timestamp":1755561600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"National Research Centre (NCN)","doi-asserted-by":"publisher","award":["UMO-2020\/37\/B\/NZ4\/03454"],"award-info":[{"award-number":["UMO-2020\/37\/B\/NZ4\/03454"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cancer-associated cachexia is a multifaceted wasting syndrome characterized by progressive loss of skeletal muscle mass, systemic inflammation, and metabolic dysfunction and is particularly prevalent in gastrointestinal cancers. Physical activity has emerged as a promising non-pharmacological intervention capable of attenuating key drivers of cachexia. Exercise modulates inflammatory signaling (e.g., IL-6\/STAT3 and TNF-\u03b1\/NF-\u03baB), enhances anabolic pathways (e.g., IGF-1\/Akt\/mTOR), and preserves lean body mass and functional capacity. Exercise-induced signaling molecules, known as exerkines, are key mediators of these benefits, which are released during physical activity and act in an autocrine, paracrine, and endocrine manner. However, many of these molecules also exhibit context-dependent effects. While they exert protective, anti-inflammatory, or anabolic actions when transiently elevated after exercise, the same molecules may contribute to cachexia pathogenesis when chronically secreted by tumors or in systemic disease states. The biological effects of a given factor depend on its origin, timing, concentration, and physiological milieu. This review presents recent evidence from clinical and experimental studies to elucidate how physical activity and exerkines may be harnessed to mitigate cancer cachexia, with particular emphasis on gastrointestinal malignancies and their unique metabolic challenges.<\/jats:p>","DOI":"10.3390\/ijms26168011","type":"journal-article","created":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T13:08:51Z","timestamp":1755608931000},"page":"8011","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Physical Activity, Exerkines, and Their Role in Cancer Cachexia"],"prefix":"10.3390","volume":"26","author":[{"given":"Jan","family":"Bilski","sequence":"first","affiliation":[{"name":"Department of Biomechanics and Kinesiology, Institute of Physiotherapy, Faculty of Health Sciences, Jagiellonian University Medical College, 31-008 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Szlachcic","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0294-5185","authenticated-orcid":false,"given":"Agata","family":"Ptak-Belowska","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5805-0065","authenticated-orcid":false,"given":"Tomasz","family":"Brzozowski","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Neshan, M., Tsilimigras, D.I., Han, X., Zhu, H., and Pawlik, T.M. 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