{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T02:32:25Z","timestamp":1791772345722,"version":"4.3.4"},"reference-count":44,"publisher":"Elsevier BV","issue":"2","license":[{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T00:00:00Z","timestamp":1767312000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003803","name":"University of Hong Kong","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003803","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001839","name":"University Grants Committee","doi-asserted-by":"publisher","award":["TRS T12-701\/17-R"],"award-info":[{"award-number":["TRS T12-701\/17-R"]}],"id":[{"id":"10.13039\/501100001839","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005407","name":"Hong Kong Health Bureau","doi-asserted-by":"publisher","award":["HMRF 06171566"],"award-info":[{"award-number":["HMRF 06171566"]}],"id":[{"id":"10.13039\/501100005407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100022720","name":"Health Bureau","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100022720","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002920","name":"Research Grants Council, University Grants Committee","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002920","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["iScience"],"published-print":{"date-parts":[[2026,2]]},"DOI":"10.1016\/j.isci.2026.114638","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T16:17:44Z","timestamp":1767802664000},"page":"114638","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":2,"title":["Patient-derived organoid xenografts model esophageal cancer cachexia and enable assessment of anti-inflammatory drug repositioning"],"prefix":"10.1016","volume":"29","author":[{"given":"Bryan Chee-chad","family":"Lung","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alvin Ka-kiu","family":"Leung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carissa Wing-Yan","family":"Wong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian Yu-hong","family":"Wong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryl Chee Heng","family":"Lung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony Wing-ip","family":"Lo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josephine Mun-Yee","family":"Ko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dora Lai-wan","family":"Kwong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Law","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Li","family":"Lung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3010-6012","authenticated-orcid":false,"given":"Valen Zhuoyou","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.isci.2026.114638_bib1","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/nrclinonc.2015.200","article-title":"Cachexia in patients with oesophageal cancer","volume":"13","author":"Anandavadivelan","year":"2016","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"10.1016\/j.isci.2026.114638_bib2","first-page":"178","article-title":"The nutritional status and immunological situation of cancer patients","volume":"7","author":"Larrea","year":"1992","journal-title":"Nutr. Hosp."},{"key":"10.1016\/j.isci.2026.114638_bib3","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s12957-018-1327-4","article-title":"Loss of skeletal muscle mass during neoadjuvant treatments correlates with worse prognosis in esophageal cancer: a retrospective cohort study","volume":"16","author":"J\u00e4rvinen","year":"2018","journal-title":"World J. Surg. Oncol."},{"key":"10.1016\/j.isci.2026.114638_bib4","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1038\/nrc3829","article-title":"Cancer cachexia: understanding the molecular basis","volume":"14","author":"Argil\u00e9s","year":"2014","journal-title":"Nat. Rev. Cancer"},{"key":"10.1016\/j.isci.2026.114638_bib5","doi-asserted-by":"crossref","DOI":"10.3390\/ijms252211945","article-title":"Metabolic, Inflammatory, and Molecular Impact of Cancer Cachexia on the Liver","volume":"25","author":"Gon\u00e7alves","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.isci.2026.114638_bib6","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1002\/ags3.12174","article-title":"Recent advancements in esophageal cancer treatment in Japan","volume":"2","author":"Tanaka","year":"2018","journal-title":"Ann. Gastroenterol. Surg."},{"key":"10.1016\/j.isci.2026.114638_bib7","doi-asserted-by":"crossref","first-page":"179","DOI":"10.2165\/00063030-200519030-00004","article-title":"The science of megestrol acetate delivery: potential to improve outcomes in cachexia","volume":"19","author":"Femia","year":"2005","journal-title":"BioDrugs"},{"key":"10.1016\/j.isci.2026.114638_bib8","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1186\/s12885-018-5080-4","article-title":"Pharmacological management of cachexia in adult cancer patients: a systematic review of clinical trials","volume":"18","author":"Advani","year":"2018","journal-title":"BMC Cancer"},{"key":"10.1016\/j.isci.2026.114638_bib9","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1097\/SPC.0000000000000233","article-title":"Animal models for cancer cachexia","volume":"10","author":"Ballar\u00f2","year":"2016","journal-title":"Curr. Opin. Supportive Palliat. Care"},{"key":"10.1016\/j.isci.2026.114638_bib10","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":"10.1016\/j.isci.2026.114638_bib11","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1038\/s42255-025-01265-2","article-title":"Hepatic gluconeogenesis and PDK3 upregulation drive cancer cachexia in flies and mice","volume":"7","author":"Liu","year":"2025","journal-title":"Nat. Metab."},{"key":"10.1016\/j.isci.2026.114638_bib12","doi-asserted-by":"crossref","DOI":"10.1016\/j.bbrc.2025.151766","article-title":"Integrative metabolic profiling of hypothalamus and skeletal muscle in a mouse model of cancer cachexia","volume":"763","author":"Choi","year":"2025","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.isci.2026.114638_bib13","article-title":"Sex-specific survival but not tissue wasting in the KPP mouse model of pancreatic cancer-induced cachexia","author":"Weinzierl","year":"2024","journal-title":"bioRxiv"},{"key":"10.1016\/j.isci.2026.114638_bib14","doi-asserted-by":"crossref","DOI":"10.4081\/ejtm.2019.7960","article-title":"Therapeutic strategies against cancer cachexia","volume":"29","author":"Argiles","year":"2019","journal-title":"Eur. J. Transl. Myol."},{"key":"10.1016\/j.isci.2026.114638_bib15","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1016\/j.ccell.2024.03.009","article-title":"The crosstalk between macrophages and cancer cells potentiates pancreatic cancer cachexia","volume":"42","author":"Liu","year":"2024","journal-title":"Cancer Cell"},{"key":"10.1016\/j.isci.2026.114638_bib16","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.canlet.2020.04.017","article-title":"Macrophages potentiate STAT3 signaling in skeletal muscles and regulate pancreatic cancer cachexia","volume":"484","author":"Shukla","year":"2020","journal-title":"Cancer Lett."},{"key":"10.1016\/j.isci.2026.114638_bib17","first-page":"4","article-title":"Patient-derived pancreatic tumour organoid implantation establishes novel pre-cachexia mouse models","volume":"6","author":"Aberle","year":"2023","journal-title":"JCSM Commun."},{"key":"10.1016\/j.isci.2026.114638_bib18","doi-asserted-by":"crossref","DOI":"10.1016\/j.canlet.2024.216999","article-title":"\u0394Np63-restricted viral mimicry response impedes cancer cell viability and remodels tumor microenvironment in esophageal squamous cell carcinoma","volume":"595","author":"Yu","year":"2024","journal-title":"Cancer Lett."},{"key":"10.1016\/j.isci.2026.114638_bib19","article-title":"Preclinical Investigation of Alpinetin in the Treatment of Cancer-Induced Cachexia via Activating PPAR\u03b3","volume":"12","author":"Zhang","year":"2021","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.isci.2026.114638_bib20","doi-asserted-by":"crossref","first-page":"2667","DOI":"10.1056\/NEJMcibr1012075","article-title":"Rosiglitazone, PPAR\u03b3, and type 2 diabetes","volume":"363","author":"Kahn","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.isci.2026.114638_bib21","doi-asserted-by":"crossref","first-page":"957","DOI":"10.4161\/cbt.12.11.18134","article-title":"Rosiglitazone delayed weight loss and anorexia while attenuating adipose depletion in mice with cancer cachexia","volume":"12","author":"Asp","year":"2011","journal-title":"Cancer Biol. Ther."},{"key":"10.1016\/j.isci.2026.114638_bib22","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1158\/1535-7163.MCT-20-0591","article-title":"CSF1\/CSF1R Signaling Inhibitor Pexidartinib (PLX3397) Reprograms Tumor-Associated Macrophages and Stimulates T-cell Infiltration in the Sarcoma Microenvironment","volume":"20","author":"Fujiwara","year":"2021","journal-title":"Mol. Cancer Ther."},{"key":"10.1016\/j.isci.2026.114638_bib23","doi-asserted-by":"crossref","first-page":"3093","DOI":"10.1200\/jco.2011.29.15_suppl.3093","article-title":"Pharmacodynamic activity demonstrated in phase I for PLX3397, a selective inhibitor of FMS and Kit","volume":"29","author":"Anthony","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"10.1016\/j.isci.2026.114638_bib24","doi-asserted-by":"crossref","first-page":"C310","DOI":"10.1152\/ajpcell.00317.2024","article-title":"Exploring heterogeneity: a dive into preclinical models of cancer cachexia","volume":"327","author":"Morena","year":"2024","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"10.1016\/j.isci.2026.114638_bib25","doi-asserted-by":"crossref","DOI":"10.1002\/jev2.12060","article-title":"Extracellular vesicles derived from oesophageal cancer containing P4HB promote muscle wasting via regulating PHGDH\/Bcl-2\/caspase-3 pathway","volume":"10","author":"Gao","year":"2021","journal-title":"J. Extracell. Vesicles"},{"key":"10.1016\/j.isci.2026.114638_bib26","doi-asserted-by":"crossref","DOI":"10.1155\/2015\/910715","article-title":"A versatile orthotopic nude mouse model for study of esophageal squamous cell carcinoma","volume":"2015","author":"Ip","year":"2015","journal-title":"BioMed Res. Int."},{"key":"10.1016\/j.isci.2026.114638_bib27","series-title":"Esophageal Abnormalities","first-page":"6","article-title":"Nutritional Management of Esophageal Cancer Patients","author":"Dimitrios","year":"2017"},{"key":"10.1016\/j.isci.2026.114638_bib28","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1007\/s11894-012-0272-6","article-title":"Nutrition therapy issues in esophageal cancer","volume":"14","author":"Miller","year":"2012","journal-title":"Curr. Gastroenterol. Rep."},{"key":"10.1016\/j.isci.2026.114638_bib29","doi-asserted-by":"crossref","first-page":"797","DOI":"10.2337\/diabetes.51.3.797","article-title":"The effects of rosiglitazone on insulin sensitivity, lipolysis, and hepatic and skeletal muscle triglyceride content in patients with type 2 diabetes","volume":"51","author":"Mayerson","year":"2002","journal-title":"Diabetes"},{"key":"10.1016\/j.isci.2026.114638_bib30","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2023.1254317","article-title":"A glimpse of the connection between PPAR\u03b3 and macrophage","volume":"14","author":"Yu","year":"2023","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.isci.2026.114638_bib31","doi-asserted-by":"crossref","first-page":"5531","DOI":"10.1158\/0008-5472.CAN-06-4585","article-title":"Mechanism of increased lipolysis in cancer cachexia","volume":"67","author":"Agustsson","year":"2007","journal-title":"Cancer Res."},{"key":"10.1016\/j.isci.2026.114638_bib32","doi-asserted-by":"crossref","first-page":"2992","DOI":"10.1172\/JCI34260","article-title":"Insulin sensitivity: modulation by nutrients and inflammation","volume":"118","author":"Schenk","year":"2008","journal-title":"J. Clin. Investig."},{"key":"10.1016\/j.isci.2026.114638_bib33","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/s40425-017-0257-y","article-title":"Colony-stimulating factor 1 receptor (CSF1R) inhibitors in cancer therapy","volume":"5","author":"Cannarile","year":"2017","journal-title":"J. Immunother. Cancer"},{"key":"10.1016\/j.isci.2026.114638_bib34","doi-asserted-by":"crossref","DOI":"10.1177\/1758835919854238","article-title":"Phase Ib study of the combination of pexidartinib (PLX3397), a CSF-1R inhibitor, and paclitaxel in patients with advanced solid tumors","volume":"11","author":"Wesolowski","year":"2019","journal-title":"Ther. Adv. Med. Oncol."},{"key":"10.1016\/j.isci.2026.114638_bib35","doi-asserted-by":"crossref","first-page":"491","DOI":"10.3389\/fimmu.2014.00491","article-title":"Macrophage cytokines: involvement in immunity and infectious diseases","volume":"5","author":"Arango Duque","year":"2014","journal-title":"Front. Immunol."},{"key":"10.1016\/j.isci.2026.114638_bib36","doi-asserted-by":"crossref","first-page":"579","DOI":"10.3390\/cells11030579","article-title":"Cytokines and Chemokines in Cancer Cachexia and Its Long-Term Impact on COVID-19","volume":"11","author":"Singh","year":"2022","journal-title":"Cells"},{"key":"10.1016\/j.isci.2026.114638_bib37","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/nature10653","article-title":"Alternatively activated macrophages produce catecholamines to sustain adaptive thermogenesis","volume":"480","author":"Nguyen","year":"2011","journal-title":"Nature"},{"key":"10.1016\/j.isci.2026.114638_bib38","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/cmi.2016.71","article-title":"IL-25 stimulates M2 macrophage polarization and thereby promotes mitochondrial respiratory capacity and lipolysis in adipose tissues against obesity","volume":"15","author":"Feng","year":"2018","journal-title":"Cell. Mol. Immunol."},{"key":"10.1016\/j.isci.2026.114638_bib39","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1016\/j.bbrc.2017.06.170","article-title":"Omega-3 fatty acids promote fatty acid utilization and production of pro-resolving lipid mediators in alternatively activated adipose tissue macrophages","volume":"490","author":"Rombaldova","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.isci.2026.114638_bib40","doi-asserted-by":"crossref","first-page":"7313","DOI":"10.3390\/ijms25137313","article-title":"Macrophages as a Source and Target of GDF-15","volume":"25","author":"Silva-Bermudez","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.isci.2026.114638_bib41","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1016\/j.tem.2020.10.004","article-title":"Insights Into Mechanisms of GDF15 and Receptor GFRAL: Therapeutic Targets","volume":"31","author":"Rochette","year":"2020","journal-title":"Trends Endocrinol. Metab."},{"key":"10.1016\/j.isci.2026.114638_bib42","doi-asserted-by":"crossref","DOI":"10.1002\/ctm2.70280","article-title":"GDF-15 blockade: A multi-directional approach to potentiate cancer immunotherapy and alleviate cancer cachexia","volume":"15","author":"Melero","year":"2025","journal-title":"Clin. Transl. Med."},{"key":"10.1016\/j.isci.2026.114638_bib43","doi-asserted-by":"crossref","first-page":"2291","DOI":"10.1056\/NEJMoa2409515","article-title":"Ponsegromab for the Treatment of Cancer Cachexia","volume":"391","author":"Groarke","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.isci.2026.114638_bib44","first-page":"273","article-title":"GDF-15\/MIC-1 a novel member of the TGF-beta superfamily","volume":"107","author":"Strelau","year":"2000","journal-title":"J. Neural. Transm. Suppl."}],"container-title":["iScience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2589004226000131?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2589004226000131?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T01:18:54Z","timestamp":1791335934000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2589004226000131"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2]]},"references-count":44,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["S2589004226000131"],"URL":"https:\/\/doi.org\/10.1016\/j.isci.2026.114638","relation":{},"ISSN":["2589-0042"],"issn-type":[{"value":"2589-0042","type":"print"}],"subject":[],"published":{"date-parts":[[2026,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Patient-derived organoid xenografts model esophageal cancer cachexia and enable assessment of anti-inflammatory drug repositioning","name":"articletitle","label":"Article Title"},{"value":"iScience","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.isci.2026.114638","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Authors. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"114638"}}