{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T07:22:18Z","timestamp":1792221738486,"version":"4.4.0"},"reference-count":114,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2021,8,6]],"date-time":"2021-08-06T00:00:00Z","timestamp":1628208000000},"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>The term \u201ccachexia\u201d is derived from the Greek words kakos (bad) and hexis (habit). Cachexia is a malnutrition associated with chronic diseases such as cancer, chronic heart failure, chronic renal failure, and autoimmune diseases, and is characterized by decreased skeletal muscle mass. Cancer cachexia is quite common in patients with advanced cancer. Weight loss is also a characteristic symptom of cancer cachexia, along with decreased skeletal muscle mass. As nutritional supplementation alone cannot improve cachexia, cytokines and tumor-derived substances have been attracting attention as its relevant factors. Cancer cachexia can be also associated with reduced chemotherapeutic effects, increased side effects and treatment interruptions, and even poorer survival. In 2011, a consensus definition of cachexia has been proposed, and the number of relevant research reports has increased significantly. However, the pathogenesis of cachexia is not fully understood, and there are currently few regulatory-approved standard treatments for cachexia. The main reason for this is that multiple etiologies are involved in the development of cachexia. In this review, we will outline the current status of cachexia, the mechanisms of which have been elucidated in recent years, especially from the perspective of advanced cancer.<\/jats:p>","DOI":"10.3390\/ijms22168491","type":"journal-article","created":{"date-parts":[[2021,8,8]],"date-time":"2021-08-08T21:49:41Z","timestamp":1628459381000},"page":"8491","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":229,"title":["Cancer Cachexia: Its Mechanism and Clinical Significance"],"prefix":"10.3390","volume":"22","author":[{"given":"Hiroki","family":"Nishikawa","sequence":"first","affiliation":[{"name":"The Second Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Takatsuki 569-8686, Japan"},{"name":"The Premier Departmental Research of Medicine, Osaka Medical and Pharmaceutical University, Takatsuki 569-8686, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4279-8682","authenticated-orcid":false,"given":"Masahiro","family":"Goto","sequence":"additional","affiliation":[{"name":"The Second Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Takatsuki 569-8686, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinya","family":"Fukunishi","sequence":"additional","affiliation":[{"name":"The Second Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Takatsuki 569-8686, Japan"},{"name":"The Premier Departmental Research of Medicine, Osaka Medical and Pharmaceutical University, Takatsuki 569-8686, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2915-7875","authenticated-orcid":false,"given":"Akira","family":"Asai","sequence":"additional","affiliation":[{"name":"The Second Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Takatsuki 569-8686, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhei","family":"Nishiguchi","sequence":"additional","affiliation":[{"name":"Kano General Hospital, Osaka 531-0041, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhide","family":"Higuchi","sequence":"additional","affiliation":[{"name":"The Second Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Takatsuki 569-8686, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,6]]},"reference":[{"key":"ref_1","first-page":"257","article-title":"What is cancer anorexia-cachexia syndrome? A historical perspective","volume":"39","author":"Walsh","year":"2009","journal-title":"J. R. Coll. Physicians Edinb."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.clnu.2009.12.004","article-title":"Consensus definition of sarcopenia, cachexia and pre-cachexia: Joint document elaborated by Special Interest Groups (SIG) \u201ccachexia-anorexia in chronic wasting diseases\u201d and \u201cnutrition in geriatrics\u201d","volume":"29","author":"Muscaritoli","year":"2010","journal-title":"Clin. Nutr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1038\/nrc3829","article-title":"Cancer cachexia: Understanding the molecular basis","volume":"14","author":"Argiles","year":"2014","journal-title":"Nat. Rev. Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"377","DOI":"10.3322\/caac.21489","article-title":"Hypercalcemia and cancer: Differential diagnosis and treatment","volume":"68","author":"Zagzag","year":"2018","journal-title":"Cancer J. Clin."},{"key":"ref_5","first-page":"159","article-title":"Pathogenesis of cancer cachexia","volume":"1","author":"Tisdale","year":"2003","journal-title":"J. Support. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.cmet.2012.06.011","article-title":"Cancer cachexia: Mediators, signaling, and metabolic pathways","volume":"16","author":"Fearon","year":"2012","journal-title":"Cell. Metab."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1101\/gad.276733.115","article-title":"Mechanisms of metabolic dysfunction in cancer-associated cachexia","volume":"30","author":"Petruzzelli","year":"2016","journal-title":"Genes Dev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1093\/ajcn\/50.5.1231","article-title":"Summary comments","volume":"50","author":"Rosenberg","year":"1989","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1111\/hepr.12774","article-title":"Japan Society of Hepatology guidelines for sarcopenia in liver disease (1st edition): Recommendation from the working group for creation of sarcopenia assessment criteria","volume":"46","author":"Nishikawa","year":"2016","journal-title":"Hepatol. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1093\/ageing\/afy169","article-title":"Sarcopenia: Revised European consensus on definition and diagnosis","volume":"48","author":"Bahat","year":"2019","journal-title":"Age Ageing"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.jamda.2019.12.012","article-title":"Asian Working Group for Sarcopenia: 2019 Consensus Update on Sar-copenia Diagnosis and Treatment","volume":"21","author":"Chen","year":"2020","journal-title":"J. Am. Med. Dir. Assoc."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1016\/j.clnu.2008.06.013","article-title":"Cachexia: A new definition","volume":"27","author":"Evans","year":"2008","journal-title":"Clin. Nutr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1016\/j.clnu.2016.03.023","article-title":"Unsatisfactory knowledge and use of terminology regarding malnutrition, starvation, cachexia and sarcopenia among dietitians","volume":"35","author":"Vanhauwaert","year":"2016","journal-title":"Clin. Nutr."},{"key":"ref_14","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_15","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1002\/jcsm.12675","article-title":"The regulatory approval of anamorelin for treatment of cachexia in patients with non-small cell lung cancer, gastric cancer, pancreatic cancer, and colorectal cancer in Japan: Facts and numbers","volume":"12","author":"Wakabayashi","year":"2021","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41389-020-00288-6","article-title":"Understanding the common mechanisms of heart and skeletal muscle wasting in cancer cachexia","volume":"10","author":"Rausch","year":"2021","journal-title":"Oncogene"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2438","DOI":"10.1200\/JCO.20.00611","article-title":"Management of Cancer Cachexia: ASCO Guideline","volume":"38","author":"Roeland","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/s13539-013-0105-y","article-title":"Cachexia as a major public health problem: Frequent, costly, and deadly","volume":"4","author":"Farkas","year":"2013","journal-title":"J. Cachex-Sarcopenia Muscle"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1016\/j.clnu.2016.12.003","article-title":"Association between cachexia, chemotherapy and outcomes in older cancer patients: A systematic review","volume":"36","author":"Caillet","year":"2017","journal-title":"Clin. Nutr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2371","DOI":"10.3892\/ijo.2015.2969","article-title":"Proposal of the performance status combined Japan Integrated Staging system in hepatocellular carcinoma complicated with cirrhosis","volume":"46","author":"Nishikawa","year":"2015","journal-title":"Int. J. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1200\/JCO.2014.56.1894","article-title":"Diagnostic Criteria for the Classification of Cancer-Associated Weight Loss","volume":"33","author":"Martin","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1007\/s00520-009-0684-5","article-title":"A descriptive review of the factors contributing to nutritional compromise in patients with head and neck cancer","volume":"17","author":"Chasen","year":"2009","journal-title":"Support. Care Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.clnu.2016.09.004","article-title":"ESPEN guidelines on definitions and terminology of clinical nutrition","volume":"36","author":"Cederholm","year":"2017","journal-title":"Clin. Nutr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1002\/jcsm.12275","article-title":"Development and validation of a clinically applicable score to classify cachexia stages in advanced cancer patients","volume":"9","author":"Zhou","year":"2018","journal-title":"J. Cachex-Sarcopenia Muscle"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1002\/jcsm.12048","article-title":"SARC-F: A symptom score to predict persons with sarcopenia at risk for poor functional outcomes","volume":"7","author":"Malmstrom","year":"2015","journal-title":"J. Cachex-Sarcopenia Muscle"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Arends, J., Strasser, F., Gonella, S., Solheim, T.S., Madeddu, C., Ravasco, P., Buonaccorso, L., de van der Schueren, M.A.E., Baldwin, C., and Chasen, M. (2021, June 02). Cancer Cachexia in Adult Patients: ESMO Clinical Practice Guidelines. Available online: https:\/\/www.esmo.org\/guidelines\/supportive-and-palliative-care\/cancer-cachexia-in-adult-patients.","DOI":"10.1016\/j.esmoop.2021.100092"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.clnu.2018.08.002","article-title":"GLIM criteria for the diagnosis of malnutrition\u2014A consensus report from the global clinical nutrition community","volume":"38","author":"Cederholm","year":"2018","journal-title":"Clin. Nutr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1002\/jhbp.455","article-title":"Clinical utility of bioimpedance analysis in liver cirrhosis","volume":"24","author":"Nishikawa","year":"2017","journal-title":"J. Hepato-Biliary-Pancreat. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Nishikawa, H., Enomoto, H., Nishiguchi, S., and Iijima, H. (2021). Sarcopenic Obesity in Liver Cirrhosis: Possible Mechanism and Clinical Impact. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22041917"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.1093\/annonc\/mdu085","article-title":"Early recognition of malnutrition and cachexia in the cancer patient: A position paper of a European School of Oncology Task Force","volume":"25","author":"Aapro","year":"2014","journal-title":"Ann. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"33","DOI":"10.21037\/apm.2018.08.04","article-title":"Health-related quality of life across cancer cachexia stages","volume":"8","author":"Kasvis","year":"2019","journal-title":"Ann. Palliat. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1016\/j.clnu.2017.06.017","article-title":"ESPEN expert group recommendations for action against cancer-related malnutrition","volume":"36","author":"Arends","year":"2017","journal-title":"Clin. Nutr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1038\/bjc.2016.3","article-title":"Identification of neutrophil-derived pro-teases and angiotensin II as biomarkers of cancer cachexia","volume":"114","author":"Penafuerte","year":"2016","journal-title":"Br. J. Cancer"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1002\/jcsm.12127","article-title":"A systematic review on the role of vitamins, minerals, proteins, and other supplements for the treatment of cachexia in cancer: A European Palliative Care Research Centre cachexia project","volume":"8","author":"Cuhls","year":"2017","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1249\/JES.0000000000000159","article-title":"Resistance Exercise\u2019s Ability to Reverse Cancer-Induced Anabolic Resistance","volume":"46","author":"Montalvo","year":"2018","journal-title":"Exerc. Sport Sci. Rev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"ii10","DOI":"10.1093\/annonc\/mdx809","article-title":"Muscle protein anabolism in advanced cancer patients: Response to protein and amino acids support, and to physical activity","volume":"29","author":"Antoun","year":"2018","journal-title":"Ann. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"17","DOI":"10.4251\/wjgo.v7.i4.17","article-title":"Cancer cachexia, mechanism and treatment","volume":"7","author":"Aoyagi","year":"2015","journal-title":"World J. Gastrointest. Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1097\/01.mco.0000165004.93707.88","article-title":"Systemic inflammation, cachexia and prognosis in patients with cancer","volume":"8","author":"Deans","year":"2005","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1016\/j.ctrv.2012.08.003","article-title":"The systemic inflammation-based Glasgow Prognostic Score: A decade of experience in patients with cancer","volume":"39","author":"McMillan","year":"2013","journal-title":"Cancer Treat. Rev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.3389\/fonc.2020.01541","article-title":"A Meta-Analysis of Glasgow Prognostic Score and Modified Glasgow Prognostic Score as Biomarkers for Predicting Survival Outcome in Renal Cell Carcinoma","volume":"10","author":"Tong","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1152\/physrev.00016.2008","article-title":"Mechanisms of Cancer Cachexia","volume":"89","author":"Tisdale","year":"2009","journal-title":"Physiol. Rev."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1038\/bjc.2014.379","article-title":"Functional identity of receptors for proteolysis-inducing factor on human and murine skeletal muscle","volume":"111","author":"Mirza","year":"2014","journal-title":"Br. J. Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"346","DOI":"10.3816\/CLC.2010.n.044","article-title":"Expression and Clinicopathologic Significance of Proteolysis-Inducing Factor in Non\u2013Small-Cell Lung Cancer: An Immunohistochemical Analysis","volume":"11","author":"Wang","year":"2010","journal-title":"Clin. Lung Cancer"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.nut.2019.03.012","article-title":"Mediators of cachexia in cancer patients","volume":"66","author":"Busquets","year":"2019","journal-title":"Nutrition"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1002\/jcsm.12376","article-title":"Muscle wasting in patients with end-stage renal disease or ear-ly-stage lung cancer: Common mechanisms at work","volume":"10","author":"Aniort","year":"2019","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1002\/jcb.26174","article-title":"Tumor Necrosis Factor-Alpha: Role in Development of Insulin Resistance and Patho-genesis of Type 2 Diabetes Mellitus","volume":"119","author":"Akash","year":"2018","journal-title":"J. Cell Biochem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1056\/NEJMcp042806","article-title":"Hypercalcemia Associated with Cancer","volume":"352","author":"Stewart","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/978-3-030-22254-3_13","article-title":"Parathyroid Hormone-Related Protein (PTHrP): An Emerging Target in Cancer Progression and Metastasis","volume":"1164","author":"Zhang","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.cmet.2014.06.011","article-title":"A Switch from White to Brown Fat Increases Energy Expenditure in Cancer-Associated Cachexia","volume":"20","author":"Petruzzelli","year":"2014","journal-title":"Cell Metab."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1210\/endrev\/bnz007","article-title":"Brown Adipose Crosstalk in Tissue Plasticity and Human Metabolism","volume":"41","author":"Scheele","year":"2019","journal-title":"Endocr. Rev."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1038\/cdd.2016.113","article-title":"Hedgehog signaling in bone regulates whole-body energy metabolism through a bone\u2013adipose endocrine relay mediated by PTHrP and adiponectin","volume":"24","author":"Zhang","year":"2016","journal-title":"Cell Death Differ."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41574-018-0123-0","article-title":"Inter-tissue communication in cancer cachexia","volume":"15","author":"Argiles","year":"2018","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"4270","DOI":"10.1200\/JCO.2016.67.4283","article-title":"Obesity and Cancer Mechanisms: Tumor Microenvironment and Inflammation","volume":"34","author":"Iyengar","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1982","DOI":"10.1002\/ijc.33418","article-title":"Tumor-secreted proliferin-1 regulates adipogenesis and lipolysis in cachexia","volume":"148","author":"Nguyen","year":"2020","journal-title":"Int. J. Cancer"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Rupert, J.E., Narasimhan, A., Jengelley, D.H., Jiang, Y., Liu, J., Au, E., Silverman, L.M., Sandusky, G., Bonetto, A., and Cao, S. (2021). Tumor-derived IL-6 and trans-signaling among tumor, fat, and muscle mediate pancreatic cancer cachexia. J. Exp. Med., 218.","DOI":"10.1084\/jem.20190450"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"33","DOI":"10.3389\/fcell.2020.00033","article-title":"Fat Wasting Is Damaging: Role of Adipose Tissue in Cancer-Associated Cachexia","volume":"8","author":"Sun","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"298","DOI":"10.3389\/fonc.2020.00298","article-title":"Management of Cancer Cachexia: Attempting to Develop New Pharmacological Agents for New Effective Therapeutic Options","volume":"10","author":"Marceca","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1002\/jnr.24589","article-title":"Neuropeptide Y in PTSD, MDD, and chronic stress: A systematic review and meta-analysis","volume":"98","author":"Tural","year":"2020","journal-title":"J. Neurosci. Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1007\/s00125-020-05327-w","article-title":"Brain JNK and metabolic disease","volume":"64","author":"Nogueiras","year":"2020","journal-title":"Diabetologia"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1159\/000501023","article-title":"Proopiomelanocortin Processing in the Hypothalamus Is Directly Regulated by Saturated Fat: Implications for the Development of Obesity","volume":"110","author":"Razolli","year":"2019","journal-title":"Neuroendocrinology"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1126\/science.abd6176","article-title":"Microbiota-modulated CART+ enteric neurons autonomously regulate blood glucose","volume":"370","author":"Muller","year":"2020","journal-title":"Science"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2179","DOI":"10.1016\/j.biocel.2013.07.016","article-title":"Control of food intake and muscle wasting in cachexia","volume":"45","author":"Amitani","year":"2013","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"80","DOI":"10.21037\/apm.2018.11.01","article-title":"Prokinetics and ghrelin for the management of cancer cachexia syndrome","volume":"8","author":"Malik","year":"2019","journal-title":"Ann. Palliat. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1002\/jcsm.12659","article-title":"Natural ghrelin in advanced cancer patients with cachexia, a case series","volume":"12","author":"Blum","year":"2021","journal-title":"J. Cachex-Sarcopenia Muscle"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Lin, T.-C., and Hsiao, M. (2021). Leptin and Cancer: Updated Functional Roles in Carcinogenesis, Therapeutic Niches, and Developments. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22062870"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1093\/annonc\/mdu178","article-title":"\u2018Pre-cachexia\u2019: A non-existing phenomenon in cancer?","volume":"25","author":"Verheul","year":"2014","journal-title":"Ann. Oncol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1097\/SPC.0000000000000176","article-title":"Multimodal management as requirement for the clinical use of anticachexia drugs\u2014A regulatory and a clinical perspective","volume":"9","author":"Borg","year":"2015","journal-title":"Curr. Opin. Support. Palliat. Care"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1038\/nrclinonc.2012.209","article-title":"Understanding the mechanisms and treatment options in cancer cachexia","volume":"10","author":"Fearon","year":"2012","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Bland, K.A., Harrison, M., Zopf, E.M., Sousa, M.S., Currow, D.C., Ely, M., Agar, M., Butcher, B.E., Vaughan, V., and Dowd, A. (2021). Quality of Life and Symptom Burden Improve in Patients Attending a Multidisciplinary Clinical Service for Cancer Cachexia: A Retrospective Observational Review. J. Pain Symptom Manag.","DOI":"10.1016\/j.jpainsymman.2021.02.034"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1111\/j.1365-277X.2011.01189.x","article-title":"Simple nutritional intervention in patients with advanced cancers of the gastrointestinal tract, non-small cell lung cancers or mesothelioma and weight loss receiving chemotherapy: A randomised controlled trial","volume":"24","author":"Baldwin","year":"2011","journal-title":"J. Hum. Nutr. Diet."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1089\/jpm.2012.0146","article-title":"The role of thalidomide and placebo for the treatment of cancer-related anorexia-cachexia symptoms: Results of a double-blind place-bo-controlled randomized study","volume":"15","author":"Yennurajalingam","year":"2012","journal-title":"J. Palliat. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.critrevonc.2014.02.005","article-title":"Dietary treatment of weight loss in patients with advanced cancer and cachexia: A systematic literature review","volume":"91","author":"Balstad","year":"2014","journal-title":"Crit. Rev. Oncol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1002\/jcsm.12055","article-title":"Exercise for cancer cachexia in adults: Executive summary of a Cochrane Collaboration systematic review","volume":"6","author":"Grande","year":"2015","journal-title":"J. Cachex-Sarcopenia Muscle"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Bourdel-Marchasson, I., Blanc-Bisson, C., Doussau, A., Germain, C., Blanc, J.F., Dauba, J., Lahmar, C., Terrebonne, E., Lecaille, C., and Ceccaldi, J. (2014). Nutritional advice in older patients at risk of malnutrition during treatment for chemotherapy: A two-year randomized con-trolled trial. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0108687"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1634\/theoncologist.2011-0133","article-title":"Physical Exercise for Cancer Patients with Advanced Disease: A Randomized Controlled Trial","volume":"16","author":"Oldervoll","year":"2011","journal-title":"Oncologist"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"b3410","DOI":"10.1136\/bmj.b3410","article-title":"Effect of a multimodal high intensity exercise intervention in cancer patients undergoing chemotherapy: Randomised controlled trial","volume":"339","author":"Adamsen","year":"2009","journal-title":"BMJ"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1200\/JCO.2006.06.209","article-title":"Impacting Quality of Life for Patients with Advanced Cancer with a Structured Multidisciplinary Intervention: A Randomized Controlled Trial","volume":"24","author":"Rummans","year":"2006","journal-title":"J. Clin. Oncol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1186\/s13014-018-1157-0","article-title":"Progressive resistance training in cachectic head and neck cancer patients undergoing radiotherapy: A randomized controlled pilot feasibility trial","volume":"13","author":"Grote","year":"2018","journal-title":"Radiat. Oncol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1016\/j.jpainsymman.2012.05.006","article-title":"A Home-Based Exercise Program to Improve Function, Fatigue, and Sleep Quality in Patients with Stage IV Lung and Colorectal Cancer: A Randomized Controlled Trial","volume":"45","author":"Cheville","year":"2013","journal-title":"J. Pain Symptom Manag."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1097\/HCR.0000000000000410","article-title":"Exercise Training in Patients With Non-Small Cell Lung Cancer During In-Hospital Chemotherapy Treatment: A randomized controlled trial","volume":"39","author":"Rutkowska","year":"2019","journal-title":"J. Cardiopulm. Rehabil. Prev."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1007\/s00520-017-3875-5","article-title":"Eight-week, multimodal exercise counteracts a progress of chemotherapy-induced peripheral neuropathy and improves bal-ance and strength in metastasized colorectal cancer patients: A randomized controlled trial","volume":"26","author":"Zimmer","year":"2018","journal-title":"Support Care Cancer"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.annonc.2019.09.002","article-title":"Cognitive behavioral therapy or graded exercise therapy compared with usual care for severe fatigue in patients with advanced cancer during treatment: A randomized controlled trial","volume":"31","author":"Poort","year":"2020","journal-title":"Ann. Oncol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"3031","DOI":"10.1007\/s00520-017-3827-0","article-title":"Safety and feasibility of exercise interventions in patients with advanced cancer: A systematic review","volume":"25","author":"Heywood","year":"2017","journal-title":"Support Care Cancer"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1016\/j.clnu.2017.05.027","article-title":"Effects of nutrition and physical exercise intervention in palliative cancer patients: A randomized controlled trial","volume":"37","author":"Uster","year":"2018","journal-title":"Clin. Nutr."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1002\/jcsm.12201","article-title":"A randomized phase II feasibility trial of a multimodal intervention for the management of cachexia in lung and pancreatic cancer","volume":"8","author":"Solheim","year":"2017","journal-title":"J. Cachex-Sarcopenia Muscle"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1136\/bmjspcare-2017-001440","article-title":"Cancer cachexia: Rationale for the MENAC (Multimodal\u2014Exercise, Nutrition and Anti-inflammatory medication for Cachexia) trial","volume":"8","author":"Solheim","year":"2018","journal-title":"BMJ Support. Palliat. Care"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"383","DOI":"10.4103\/apjon.apjon_21_18","article-title":"Promotion of Behavioral Change and the Impact on Quality of Life in Elderly Patients with Advanced Cancer: A Physical Activity Intervention of the Multimodal Nutrition and Exercise Treatment for Advanced Cancer Program","volume":"5","author":"Naito","year":"2018","journal-title":"Asia-Pac. J. Oncol. Nurs."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/jcsm.12351","article-title":"Feasibility of early multi-modal interventions for elderly patients with advanced pancreatic and non-small-cell lung cancer","volume":"10","author":"Naito","year":"2019","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2898","DOI":"10.1016\/j.clnu.2021.02.005","article-title":"ESPEN practical guideline: Clinical Nutrition in cancer","volume":"40","author":"Muscaritoli","year":"2021","journal-title":"Clin. Nutr."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1002\/ijc.1332","article-title":"Dietary intake and resting energy expenditure in relation to weight loss in unselected cancer patients","volume":"93","author":"Bosaeus","year":"2001","journal-title":"Int. J. Cancer"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.clnu.2009.07.001","article-title":"Resting energy expenditure and body com-position in patients with newly detected cancer","volume":"29","author":"Cao","year":"2010","journal-title":"Clin. Nutr."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/j.suc.2011.04.007","article-title":"Nutrition and gut immunity","volume":"91","author":"Fukatsu","year":"2011","journal-title":"Surg. Clin. N. Am."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1016\/j.clnu.2020.07.027","article-title":"Effects of enteral nutrition and parenteral nutrition on survival in patients with advanced cancer cachexia: Analysis of a multicenter prospective cohort study","volume":"40","author":"Amano","year":"2021","journal-title":"Clin. Nutr."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.clnu.2012.10.017","article-title":"Is the intravenous supplementation of amino acid to cancer patients adequate? A critical appraisal of literature","volume":"32","author":"Bozzetti","year":"2013","journal-title":"Clin. Nutr."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/j.clnu.2011.05.008","article-title":"Muscle protein synthesis in cancer patients can be stimulated with a specially formulated medical food","volume":"30","author":"Deutz","year":"2011","journal-title":"Clin. Nutr."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/j.annonc.2020.02.016","article-title":"Cancer-related fatigue: ESMO Clinical Practice Guidelines for diagnosis and treatment","volume":"31","author":"Fabi","year":"2020","journal-title":"Ann. Oncol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"6","DOI":"10.3109\/0284186X.2012.724536","article-title":"Non-steroidal anti-inflammatory treatment in cancer cachexia: A systematic literature review","volume":"52","author":"Solheim","year":"2012","journal-title":"Acta Oncol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"3299","DOI":"10.1200\/JCO.1999.17.10.3299","article-title":"Randomized comparison of megestrol acetate versus dexamethasone versus fluoxymesterone for the treatment of cancer anorexia\/cachexia","volume":"17","author":"Loprinzi","year":"1999","journal-title":"J. Clin. Oncol."},{"key":"ref_99","first-page":"CD004310","article-title":"Megestrol acetate for treatment of ano-rexia-cachexia syndrome","volume":"2013","author":"Carbonell","year":"2013","journal-title":"Cochrane Database Syst Rev."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"3394","DOI":"10.1200\/JCO.2005.05.1847","article-title":"Comparison of Orally Administered Cannabis Extract and Delta-9-Tetrahydrocannabinol in Treating Patients with Cancer-Related Anorexia-Cachexia Syndrome: A Multicenter, Phase III, Randomized, Double-Blind, Placebo-Controlled Clinical Trial from the Cannabis-In-Cachexia-Study-Group","volume":"24","author":"Strasser","year":"2006","journal-title":"J. Clin. Oncol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/S1470-2045(13)70055-X","article-title":"Effects of enobosarm on muscle wasting and physical function in patients with cancer: A double-blind, randomised controlled phase 2 trial","volume":"14","author":"Dobs","year":"2013","journal-title":"Lancet Oncol."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Advani, S.M., Advani, P.G., VonVille, H.M., and Jafri, S.H. (2018). Pharmacological management of cachexia in adult cancer patients: A systematic review of clinical trials. BMC Cancer, 18.","DOI":"10.1186\/s12885-018-5080-4"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/S1470-2045(15)00558-6","article-title":"Anamorelin in patients with non-small-cell lung cancer and cachexia (ROMANA 1 and ROMANA 2): Results from two randomised, double-blind, phase 3 trials","volume":"17","author":"Temel","year":"2016","journal-title":"Lancet Oncol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1002\/cncr.31128","article-title":"Anamorelin (ONO-7643) for the treatment of patients with non-small cell lung cancer and cachexia: Results from a randomized, double-blind, placebo-controlled, multicenter study of Japanese patients (ONO-7643-04)","volume":"124","author":"Katakami","year":"2017","journal-title":"Cancer"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"4294","DOI":"10.1002\/cncr.32406","article-title":"A multicenter, open-label, single-arm study of anamorelin (ONO-7643) in advanced gastrointestinal cancer patients with cancer cachexia","volume":"125","author":"Hamauchi","year":"2019","journal-title":"Cancer"},{"key":"ref_106","first-page":"199","article-title":"Clinical results in cachexia therapeutics","volume":"19","author":"Crawford","year":"2016","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/S1470-2045(17)30006-2","article-title":"MABp1 as a novel antibody treatment for advanced colorectal cancer: A randomised, double-blind, placebo-controlled, phase 3 study","volume":"18","author":"Hickish","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1097\/00126334-200404010-00006","article-title":"Serono 9037 Study Team Growth Hormone Improves Lean Body Mass, Physical Performance, and Quality of Life in Subjects With HIV-Associated Weight Loss or Wasting on Highly Active Antiretroviral Therapy","volume":"35","author":"Moyle","year":"2004","journal-title":"JAIDS J. Acquir. Immune Defic. Syndr."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"18224","DOI":"10.18632\/oncotarget.24804","article-title":"Increased gut permeability in cancer cachexia: Mechanisms and clinical relevance","volume":"9","author":"Bindels","year":"2018","journal-title":"Oncotarget"},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Di Renzo, L., Gualtieri, P., Romano, L., Marrone, G., Noce, A., Pujia, A., Perrone, M.A., Aiello, V., Colica, C., and De Lorenzo, A. (2019). Role of Personalized Nutrition in Chronic-Degenerative Diseases. Nutrients, 11.","DOI":"10.3390\/nu11081707"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1007\/s00520-015-2958-4","article-title":"Nutrition intervention approaches to reduce malnutrition in oncology patients: A systematic review","volume":"24","author":"Lee","year":"2015","journal-title":"Support. Care Cancer"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/j.clnu.2020.05.050","article-title":"Feasibility of a multimodal intervention on malnutrition in patients with lung cancer during primary anti-neoplastic treatment","volume":"40","author":"Tobberup","year":"2021","journal-title":"Clin. Nutr."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"602775","DOI":"10.3389\/fnut.2020.602775","article-title":"Power Comparisons and Clinical Meaning of Outcome Measures in Assessing Treatment Effect in Cancer Cachexia: Secondary Analysis from a Randomized Pilot Multimodal Intervention Trial","volume":"7","author":"Balstad","year":"2021","journal-title":"Front. Nutr."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1080\/14737140.2021.1927720","article-title":"A multimodal approach to cancer-related cachexia: From theory to practice","volume":"21","author":"Avancini","year":"2021","journal-title":"Expert Rev. Anticancer Ther."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/16\/8491\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:42:01Z","timestamp":1760164921000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/16\/8491"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,6]]},"references-count":114,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["ijms22168491"],"URL":"https:\/\/doi.org\/10.3390\/ijms22168491","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,6]]}}}