{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T10:34:35Z","timestamp":1787567675642,"version":"build-2736575974"},"reference-count":81,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T00:00:00Z","timestamp":1787443200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Cancer cachexia is a multifactorial systemic syndrome characterized by progressive muscle loss, with or without adipose tissue depletion, that cannot be reversed by conventional nutritional support. It affects cancer patients and is associated with reduced treatment tolerance, impaired physical function, poor quality of life, and increased mortality. The understanding of cachexia has evolved recently, from the perception of a simple nutritional disorder to a complex immune\u2013metabolic syndrome, based on tumor\u2013host interactions, systemic inflammation, metabolic dysregulation, and multi-organ dysfunction. This review summarizes the progression of cachexia research, highlighting key findings involving inflammatory cytokines, proteolytic pathways, mitochondrial dysfunction, and immune dysregulation. The development of therapeutic strategies is examined, from early nutritional and appetite-stimulating interventions to contemporary targeted therapies, including ghrelin receptor agonists, cytokine inhibitors, and anabolic agents. Despite advances in mechanistic understanding, numerous trials targeting single pathways have failed to produce meaningful functional or survival benefits, underscoring the limitations of reductionist approaches. Emerging evidence supports a paradigm shift toward multimodal, biomarker-guided, and patient-centered interventions that address the interconnected biological mechanisms underlying cachexia. Particular emphasis is given to novel immunomodulatory strategies, including agents such as R-ketorolac, which may restore immune homeostasis and target the root causes of cachexia. It is hypothesized that future therapeutic success will likely depend on integrated approaches combining immunological, metabolic, nutritional, and rehabilitative interventions.<\/jats:p>","DOI":"10.3390\/cancers18172738","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T09:20:02Z","timestamp":1787563202000},"page":"2738","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cancer Cachexia Research and Drug Development: Lessons from Failures and the Promise of Immunomodulation"],"prefix":"10.3390","volume":"18","author":[{"given":"Lingbing","family":"Zhang","sequence":"first","affiliation":[{"name":"Yinuoke Ltd., Changchun 130012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4762-9466","authenticated-orcid":false,"given":"Jeffrey A.","family":"Norton","sequence":"additional","affiliation":[{"name":"Department of Surgery, School of Medicine, Stanford University, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Law, M.L. (2022). Cancer cachexia: Pathophysiology and association with cancer-related pain. Front. Pain Res., 3.","DOI":"10.3389\/fpain.2022.971295"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Nishikawa, H., Goto, M., Fukunishi, S., Asai, A., Nishiguchi, S., and Higuchi, K. (2021). Cancer cachexia: Its mechanism and clinical significance. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22168491"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S81","DOI":"10.1016\/j.ejphar.2011.07.007","article-title":"Anti-inflammatory therapies in cancer cachexia","volume":"668","author":"Busquets","year":"2011","journal-title":"Eur. J. Pharmacol."},{"key":"ref_4","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_5","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1038\/nrc3829","article-title":"Cancer cachexia: Understanding the molecular basis","volume":"14","author":"Busquets","year":"2014","journal-title":"Nat. Rev. Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Zhang, L., and Bonomi, P.D. (2024). Immune system disorder and cancer-associated cachexia. Cancers, 16.","DOI":"10.20944\/preprints202404.0796.v1"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"5597","DOI":"10.2147\/CMAR.S261585","article-title":"Cancer cachexia: Definition, staging, and emerging treatments","volume":"12","author":"Ni","year":"2020","journal-title":"Cancer Manag. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1177\/1758834017698643","article-title":"Cancer-induced muscle wasting: Latest findings in prevention and treatment","volume":"9","author":"Aversa","year":"2017","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_9","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_10","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1001\/archsurg.1989.01410010104021","article-title":"Cachectin activity in the serum of cachectic, tumor-bearing rats","volume":"124","author":"Stovroff","year":"1989","journal-title":"Arch. Surg."},{"key":"ref_11","first-page":"4567","article-title":"Cachectin\/tumor necrosis factor: A possible mediator of cancer anorexia in the rat","volume":"48","author":"Stovroff","year":"1988","journal-title":"Cancer Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1016\/0022-4804(89)90161-3","article-title":"Altered macrophage activity and tumor necrosis factor: Tumor necrosis and host cachexia","volume":"46","author":"Stovroff","year":"1989","journal-title":"J. Surg. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1612","DOI":"10.1016\/j.celrep.2019.07.016","article-title":"Modeling human cancer-induced cachexia","volume":"28","author":"Talbert","year":"2019","journal-title":"Cell Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.molmed.2013.02.006","article-title":"The role of triglyceride lipases in cancer associated cachexia","volume":"19","author":"Das","year":"2013","journal-title":"Trends Mol. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5280","DOI":"10.3390\/nu6115280","article-title":"Evidence and mechanisms of fat depletion in cancer","volume":"6","author":"Ebadi","year":"2014","journal-title":"Nutrients"},{"key":"ref_16","first-page":"5547","article-title":"Parabiotic transfer of cancer anorexia\/cachexia in male rats","volume":"45","author":"Norton","year":"1985","journal-title":"Cancer Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"50S","DOI":"10.1177\/014860719201600603","article-title":"Cytokines and their role in the pathophysiology of cancer cachexia","volume":"16","author":"Mcnamara","year":"1992","journal-title":"J. Parenter. Enter. Nutr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1038\/320584a0","article-title":"Cachectin and tumour necrosis factor as two sides of the same biological coin","volume":"320","author":"Beutler","year":"1986","journal-title":"Nature"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/S0889-8588(18)30457-X","article-title":"Mechanisms of cancer cachexia","volume":"5","author":"Langstein","year":"1991","journal-title":"Hematol.\/Oncol. Clin. North Am."},{"key":"ref_20","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_21","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/s13045-023-01454-0","article-title":"Cancer cachexia: Molecular mechanisms and treatment strategies","volume":"16","author":"Setiawan","year":"2023","journal-title":"J. Hematol. Oncol."},{"key":"ref_22","first-page":"68","article-title":"The immunological regulation of cancer cachexia and its therapeutic implications","volume":"5","author":"Miller","year":"2019","journal-title":"J. Cancer Metastasis Treat."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Rounis, K., Makrakis, D., Gioulbasanis, I., Ekman, S., De Petris, L., Mavroudis, D., and Agelaki, S. (2022). Cancer cachexia and antitumor immunity: Common mediators and potential targets for new therapies. Life, 12.","DOI":"10.3390\/life12060880"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Zhang, D., Zheng, H., Zhou, Y., Tang, X., Yu, B., and Li, J. (2007). Association of IL-1beta gene polymorphism with cachexia from locally advanced gastric cancer. BMC Cancer, 7.","DOI":"10.1186\/1471-2407-7-45"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.clnu.2011.07.010","article-title":"Is IL-6 the best pro-inflammatory biomarker of clinical outcomes of cancer cachexia?","volume":"31","author":"Watt","year":"2012","journal-title":"Clin. Nutr."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"R\u00e9b\u00e9, C., and Ghiringhelli, F. (2020). Interleukin-1\u03b2 and cancer. Cancers, 12.","DOI":"10.3390\/cancers12071791"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2449","DOI":"10.1084\/jem.20111020","article-title":"Central nervous system inflammation induces muscle atrophy via activation of the hypothalamic\u2013pituitary\u2013adrenal axis","volume":"208","author":"Braun","year":"2011","journal-title":"J. Exp. Med."},{"key":"ref_28","first-page":"1490","article-title":"Regulation of hepatic cardiolipin metabolism by TNF\u03b1: Implication in cancer cachexia","volume":"1851","author":"Peyta","year":"2015","journal-title":"Biochim. Biophys. Acta (BBA) -Mol. Cell Biol. Lipids"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"188359","DOI":"10.1016\/j.bbcan.2020.188359","article-title":"Advances in cancer cachexia: Intersection between affected organs, mediators, and pharmacological interventions","volume":"1873","author":"Siddiqui","year":"2020","journal-title":"Biochim. Biophys. Acta (BBA) -Rev. Cancer"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1002\/rco2.30","article-title":"Mediators and clinical treatment for cancer cachexia: A systematic review","volume":"4","author":"Cao","year":"2021","journal-title":"JCSM Rapid Commun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"462","DOI":"10.3892\/ol.2023.14049","article-title":"Role of growth differentiation factor 15 in cancer cachexia","volume":"26","author":"Ling","year":"2023","journal-title":"Oncol. Lett."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1615\/CritRevImmunol.2016017387","article-title":"Metabolic regulation of natural killer cell IFN-\u03b3 production","volume":"36","author":"Mah","year":"2016","journal-title":"Crit. Rev.\u2122 Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s40364-020-00228-x","article-title":"Roles of IFN-\u03b3 in tumor progression and regression: A review","volume":"8","author":"Jorgovanovic","year":"2020","journal-title":"Biomark. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1002\/jcsm.12346","article-title":"Tumour-derived leukaemia inhibitory factor is a major driver of cancer cachexia and morbidity in C26 tumour-bearing mice","volume":"9","author":"Kandarian","year":"2018","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Zeng, R., Tong, C., and Xiong, X. (2022). The Molecular Basis and Therapeutic Potential of Leukemia Inhibitory Factor in Cancer Cachexia. Cancers, 14.","DOI":"10.3390\/cancers14122955"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"19976","DOI":"10.1074\/jbc.M115.638411","article-title":"A key role for leukemia inhibitory factor in C26 cancer cachexia","volume":"290","author":"Seto","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.trecan.2022.01.004","article-title":"Emerging signaling mediators in the anorexia\u2013cachexia syndrome of cancer","volume":"8","author":"Talbert","year":"2022","journal-title":"Trends Cancer"},{"key":"ref_38","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_39","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1002\/jcsm.12059","article-title":"Pathophysiology of anorexia in the cancer cachexia syndrome","volume":"6","author":"Ezeoke","year":"2015","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1016\/S0899-9007(00)00413-5","article-title":"Central nervous system mechanisms contributing to the cachexia\u2013anorexia syndrome","volume":"16","year":"2000","journal-title":"Nutrition"},{"key":"ref_41","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_42","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1038\/s41577-021-00624-w","article-title":"The interplay of immunology and cachexia in infection and cancer","volume":"22","author":"Baazim","year":"2022","journal-title":"Nat. Rev. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Van de Worp, W.R., Schols, A.M., Theys, J., Van Helvoort, A., and Langen, R.C. (2020). Nutritional interventions in cancer cachexia: Evidence and perspectives from experimental models. Front. Nutr., 7.","DOI":"10.3389\/fnut.2020.601329"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"VanderVeen, B.N., Murphy, E.A., and Carson, J.A. (2020). The Impact of Immune Cells on the Skeletal Muscle Microenvironment During Cancer Cachexia. Front. Physiol., 11.","DOI":"10.3389\/fphys.2020.01037"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/s41467-020-20123-1","article-title":"Mechanisms of muscle atrophy and hypertrophy: Implications in health and disease","volume":"12","author":"Sartori","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2866","DOI":"10.1007\/s12094-024-03502-8","article-title":"SEOM clinical guidelines for cancer anorexia-cachexia syndrome (2023)","volume":"26","year":"2024","journal-title":"Clin. Transl. Oncol."},{"key":"ref_47","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. Prim."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1007\/s11914-022-00752-9","article-title":"Role of the gut microbiome in skeletal muscle physiology and pathophysiology","volume":"20","author":"Lefevre","year":"2022","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s12263-025-00791-8","article-title":"Gut microbiota in cancer cachexia: A new frontier for research and therapy","volume":"20","author":"Ardis","year":"2025","journal-title":"Genes Nutr."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1146\/annurev-cancerbio-030419-033642","article-title":"Cancer-associated cachexia: A systemic consequence of cancer progression","volume":"4","author":"Biswas","year":"2020","journal-title":"Annu. Rev. Cancer Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"ii1","DOI":"10.1093\/annonc\/mdx810","article-title":"Sarcopenic obesity: Hidden muscle wasting and its impact for survival and complications of cancer therapy","volume":"29","author":"Baracos","year":"2018","journal-title":"Ann. Oncol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Permuth, J.B., Park, M.A., Chen, D.-T., Basinski, T., Powers, B.D., Gwede, C.K., Dezsi, K.B., Gomez, M., Vyas, S.L., and Biachi, T. (2024). Leveraging real-world data to predict cancer cachexia stage, quality of life, and survival in a racially and ethnically diverse multi-institutional cohort of treatment-na\u00efve patients with pancreatic ductal adenocarcinoma. Front. Oncol., 14.","DOI":"10.3389\/fonc.2024.1362244"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1097\/SPC.0000000000000398","article-title":"Targeting IL-1\u03b1 in cancer cachexia: A narrative review","volume":"12","author":"McDonald","year":"2018","journal-title":"Curr. Opin. Support. Palliat. Care"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1007\/s11912-024-01549-y","article-title":"Anamorelin for the treatment of cancer anorexia-cachexia syndrome","volume":"26","author":"Dev","year":"2024","journal-title":"Curr. Oncol. Rep."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1038\/s41571-023-00734-5","article-title":"Cancer-associated cachexia\u2014Understanding the tumour macroenvironment and microenvironment to improve management","volume":"20","author":"Stemmler","year":"2023","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1127704","DOI":"10.3389\/fimmu.2023.1127704","article-title":"Immunomodulation-a general review of the current state-of-the-art and new therapeutic strategies for targeting the immune system","volume":"14","author":"Strzelec","year":"2023","journal-title":"Front Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1016\/j.ccell.2026.03.012","article-title":"Cancer cachexia: A tumor-driven disorder of whole-body homeostasis","volume":"44","author":"Zhang","year":"2026","journal-title":"Cancer Cell"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Clemente-Su\u00e1rez, V.J., Redondo-Fl\u00f3rez, L., Rubio-Zarapuz, A., Mart\u00ednez-Guardado, I., Navarro-Jim\u00e9nez, E., and Tornero-Aguilera, J.F. (2022). Nutritional and exercise interventions in cancer-related cachexia: An extensive narrative review. Int. J. Environ. Res. Public Health, 19.","DOI":"10.3390\/ijerph19084604"},{"key":"ref_59","first-page":"74","article-title":"Megestrol acetate in cancer patients with anorexia-cachexia syndrome: A meta-analysis","volume":"2","author":"Zhan","year":"2013","journal-title":"Transl. Cancer Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"178","DOI":"10.2174\/0929867329666220525124818","article-title":"Efficacy of cannabis and its constituents in disease management: Insights from clinical studies","volume":"30","author":"Vimal","year":"2023","journal-title":"Curr. Med. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1186\/s12943-025-02379-7","article-title":"Bridging the tumor microenvironment: The pivotal role of cancer-associated fibroblasts in tumor cachexia development","volume":"24","author":"Chen","year":"2025","journal-title":"Mol. Cancer"},{"key":"ref_62","first-page":"287","article-title":"Interleukin 6\/interleukin 6 receptor interaction and its role as a therapeutic target for treatment of cachexia and cancer","volume":"7","author":"Weidle","year":"2010","journal-title":"Cancer Genom. Proteom."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/S1470-2045(14)71154-4","article-title":"Anamorelin for patients with cancer cachexia: An integrated analysis of two phase 2, randomised, placebo-controlled, double-blind trials","volume":"16","author":"Garcia","year":"2015","journal-title":"Lancet Oncol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1016\/j.trecan.2025.06.007","article-title":"GDF15: From biomarker to target in cancer cachexia","volume":"11","author":"Kleinert","year":"2025","journal-title":"Trends Cancer"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Pandey, S., Bradley, L., and Del Fabbro, E. (2024). Updates in cancer cachexia: Clinical management and pharmacologic interventions. Cancers, 16.","DOI":"10.3390\/cancers16091696"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1080\/14656566.2021.1873954","article-title":"An overview of anamorelin as a treatment option for cancer-associated anorexia and cachexia","volume":"22","author":"Fonseca","year":"2021","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_67","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_68","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1002\/cncr.22944","article-title":"A placebo-controlled double blind trial of etanercept for the cancer anorexia\/weight loss syndrome: Results from N00C1 from the North Central Cancer Treatment Group","volume":"110","author":"Jatoi","year":"2007","journal-title":"Cancer"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"679","DOI":"10.21037\/apm.2018.07.06","article-title":"Anti-cytokines in the treatment of cancer cachexia","volume":"8","author":"Prado","year":"2019","journal-title":"Ann. Palliat. Med."},{"key":"ref_70","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_71","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1038\/s41392-025-02331-7","article-title":"Cancer cachexia: Molecular basis and therapeutic advances","volume":"11","author":"Tan","year":"2026","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1002\/jcsm.13435","article-title":"Phase 2 study of the efficacy and safety of ponsegromab in patients with cancer cachexia: PROACC-1 study design","volume":"15","author":"Groarke","year":"2024","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_73","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_74","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":"2013","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Wen, Y., Zhu, Y., Zhang, C., Yang, X., Gao, Y., Li, M., Yang, H., Liu, T., and Tang, H. (2022). Chronic inflammation, cancer development and immunotherapy. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.1040163"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1007\/s10238-026-02066-x","article-title":"Cytokine-Mediated tumor sensitization: Mechanistic frameworks and therapeutic opportunities in cancer Immunotherapy","volume":"26","author":"Aghaei","year":"2026","journal-title":"Clin. Exp. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1097\/MS9.0000000000004621","article-title":"Immunomodulatory strategies for managing cytokine storms in chronic COVID: Mechanisms, therapeutic targets, and clinical advances","volume":"88","author":"Obeagu","year":"2025","journal-title":"Ann. Med. Surg."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1002\/jcsm.13422","article-title":"R-ketorolac ameliorates cancer-associated cachexia and prolongs survival of tumour-bearing mice","volume":"15","author":"Chrysostomou","year":"2024","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_79","first-page":"349","article-title":"Relationships of emerging biomarkers of cancer cachexia with quality of life, appetite, and cachexia","volume":"32","author":"Lipshitz","year":"2024","journal-title":"Support. Care Cancer"},{"key":"ref_80","first-page":"2070","article-title":"Cancer cachexia: Biomarkers and the influence of age","volume":"18","author":"Geppert","year":"2024","journal-title":"Mol. Oncol."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Marceca, G.P., Londhe, P., and Calore, F. (2020). Management of Cancer Cachexia: Attempting to Develop New Pharmacological Agents for New Effective Therapeutic Options. Front. 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