{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T19:57:19Z","timestamp":1791489439876,"version":"4.3.4"},"reference-count":150,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,3,12]],"date-time":"2021-03-12T00:00:00Z","timestamp":1615507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>During its evolution, cancer induces changes in patients\u2019 energy metabolism that strongly affect the overall clinical state and are responsible for cancer-related cachexia syndrome. To better understand the mechanisms underlying cachexia and its metabolic derangements, research efforts should focus on the events that are driven by the immune system activation during the evolution of neoplastic disease and on the phenomena of \u201cresistance\u201d and \u201ctolerance\u201d typically involved in the human body response against stress, pathogens, or cancer. Indeed, in the case where resistance is not able to eliminate the cancer, tolerance mechanisms can utilize the symptoms of cachexia (anemia, anorexia, and fatigue) to counteract unregulated cancer growth. These notions are also sustained by the evidence that cancer cachexia may be reversible if the resistance and tolerance phases are supported by appropriate antineoplastic treatments. Accordingly, there is no doubt that anticachectic therapies have an irreplaceable role in cases of reversible cancer cachexia where, if harmoniously associated with effective antineoplastic therapies, they can contribute to preserve the quality of life and improve prognosis. Such anticachectic treatments should be based on targeting the complex immunological, inflammatory, and metabolic pathways involved in the complex pathogenesis of cachexia. Meanwhile, the role of the anticachectic therapies is very different in the stage of irreversible cachexia when the available antineoplastic treatments are not able to control the disease and the resistance mechanisms fail with the prevalence of the tolerance phenomena. At this stage, they can be useful only to improve the quality of life, allowing the patient and their family to get a better awareness of the final phases of life, thereby opening to the best spiritual remodulation of the final event, death.<\/jats:p>","DOI":"10.3390\/ijms22062890","type":"journal-article","created":{"date-parts":[[2021,3,12]],"date-time":"2021-03-12T11:56:55Z","timestamp":1615550215000},"page":"2890","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Cachexia as Evidence of the Mechanisms of Resistance and Tolerance during the Evolution of Cancer Disease"],"prefix":"10.3390","volume":"22","author":[{"given":"Antonio","family":"Maccio","sequence":"first","affiliation":[{"name":"Department of Gynecologic Oncology, Businco Hospital, ARNAS G. Brotzu, 09121 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Sanna","sequence":"additional","affiliation":[{"name":"Department of Gynecologic Oncology, Businco Hospital, ARNAS G. Brotzu, 09121 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Neri","sequence":"additional","affiliation":[{"name":"Department of Gynecologic Oncology, Businco Hospital, ARNAS G. Brotzu, 09121 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Oppi","sequence":"additional","affiliation":[{"name":"Hematology and Transplant Center, Businco Hospital, ARNAS G. Brotzu, 09121 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clelia","family":"Madeddu","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences and Public Health, University of Cagliari, 09124 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1007\/s00109-013-1080-7","article-title":"The role of interleukin-6 in the evolution of ovarian cancer: Clinical and prognostic implications\u2013A review","volume":"91","author":"Madeddu","year":"2013","journal-title":"J. Mol. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"17105","DOI":"10.1038\/nrdp.2017.105","article-title":"Cancer-associated cachexia","volume":"4","author":"Baracos","year":"2018","journal-title":"Nat. Rev. Dis. 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