{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:39:20Z","timestamp":1790959160473,"version":"4.1.0"},"reference-count":146,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2022,8,28]],"date-time":"2022-08-28T00:00:00Z","timestamp":1661644800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CCA Foundation 2018","award":["IG-24444"],"award-info":[{"award-number":["IG-24444"]}]},{"name":"CCA Foundation 2018","award":["IG-19927"],"award-info":[{"award-number":["IG-19927"]}]},{"name":"CCA Foundation 2018","award":["G-20074"],"award-info":[{"award-number":["G-20074"]}]},{"name":"CCA Foundation 2018","award":["#11957"],"award-info":[{"award-number":["#11957"]}]},{"name":"KWF Dutch Cancer Society","award":["IG-24444"],"award-info":[{"award-number":["IG-24444"]}]},{"name":"KWF Dutch Cancer Society","award":["IG-19927"],"award-info":[{"award-number":["IG-19927"]}]},{"name":"KWF Dutch Cancer Society","award":["G-20074"],"award-info":[{"award-number":["G-20074"]}]},{"name":"KWF Dutch Cancer Society","award":["#11957"],"award-info":[{"award-number":["#11957"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Cachexia is a metabolic syndrome consisting of massive loss of muscle mass and function that has a severe impact on the quality of life and survival of cancer patients. Up to 20% of lung cancer patients and up to 80% of pancreatic cancer patients are diagnosed with cachexia, leading to death in 20% of them. The main drivers of cachexia are cytokines such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-\u03b1), macrophage inhibitory cytokine 1 (MIC-1\/GDF15) and transforming growth factor-beta (TGF-\u03b2). Besides its double-edged role as a tumor suppressor and activator, TGF-\u03b2 causes muscle loss through myostatin-based signaling, involved in the reduction in protein synthesis and enhanced protein degradation. Additionally, TGF-\u03b2 induces inhibin and activin, causing weight loss and muscle depletion, while MIC-1\/GDF15, a member of the TGF-\u03b2 superfamily, leads to anorexia and so, indirectly, to muscle wasting, acting on the hypothalamus center. Against this background, the blockade of TGF-\u03b2 is tested as a potential mechanism to revert cachexia, and antibodies against TGF-\u03b2 reduced weight and muscle loss in murine models of pancreatic cancer. This article reviews the role of the TGF-\u03b2 pathway and to a minor extent of other molecules including microRNA in cancer onset and progression with a special focus on their involvement in cachexia, to enlighten whether TGF-\u03b2 and such other players could be potential targets for therapy.<\/jats:p>","DOI":"10.3390\/cells11172671","type":"journal-article","created":{"date-parts":[[2022,8,28]],"date-time":"2022-08-28T21:22:56Z","timestamp":1661721776000},"page":"2671","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Transforming Growth Factor-Beta Signaling in Cancer-Induced Cachexia: From Molecular Pathways to the Clinics"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4368-6973","authenticated-orcid":false,"given":"Rita","family":"Balsano","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands"},{"name":"Medical Oncology Unit, University Hospital of Parma, 43100 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9098-9312","authenticated-orcid":false,"given":"Zita","family":"Kruize","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Lunardi","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6930-0595","authenticated-orcid":false,"given":"Annalisa","family":"Comandatore","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands"},{"name":"General Surgery Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2947-9209","authenticated-orcid":false,"given":"Mara","family":"Barone","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3752-1868","authenticated-orcid":false,"given":"Andrea","family":"Cavazzoni","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1502-9108","authenticated-orcid":false,"given":"Andrea David","family":"Re Cecconi","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7742-9556","authenticated-orcid":false,"given":"Luca","family":"Morelli","sequence":"additional","affiliation":[{"name":"General Surgery Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanneke","family":"Wilmink","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9553-8465","authenticated-orcid":false,"given":"Marcello","family":"Tiseo","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit, University Hospital of Parma, 43100 Parma, Italy"},{"name":"Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid","family":"Garajov\u00e0","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit, University Hospital of Parma, 43100 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lia","family":"van Zuylen","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7565-7504","authenticated-orcid":false,"given":"Elisa","family":"Giovannetti","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands"},{"name":"Fondazione Pisana per La Scienza, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1613-9352","authenticated-orcid":false,"given":"Rosanna","family":"Piccirillo","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1152\/physiol.00019.2005","article-title":"Molecular Pathways Leading to Cancer Cachexia","volume":"20","author":"Tisdale","year":"2005","journal-title":"Physiology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/S1470-2045(10)70218-7","article-title":"Definition and Classification of Cancer Cachexia: An International Consensus","volume":"12","author":"Fearon","year":"2011","journal-title":"Lancet Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/s00520-002-0408-6","article-title":"The \u201cCancer Cachectic Factor","volume":"11","author":"Tisdale","year":"2003","journal-title":"\u201d Supportive Care 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