{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T05:23:49Z","timestamp":1793856229625,"version":"4.6.1"},"reference-count":31,"publisher":"Elsevier BV","issue":"5","license":[{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T00:00:00Z","timestamp":1742342400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100021856","name":"Ministero dell'Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100021856","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["esmoopen.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["ESMO Open"],"published-print":{"date-parts":[[2025,5]]},"DOI":"10.1016\/j.esmoop.2025.105049","type":"journal-article","created":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T14:41:35Z","timestamp":1744296095000},"page":"105049","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":27,"title":["Claudin 18.2: a promising actionable target in biliary tract cancers"],"prefix":"10.1016","volume":"10","author":[{"given":"V.","family":"Angerilli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Sacchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Rizzato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Gasparello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Ceccon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Sabbadin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Niero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Bergamo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"U.","family":"Cillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Franzina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Luchini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.P.","family":"Dei Tos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Lonardi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Fassan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"10272","key":"10.1016\/j.esmoop.2025.105049_bib1","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1016\/S0140-6736(21)00153-7","article-title":"Biliary tract cancer","volume":"397","author":"Valle","year":"2021","journal-title":"Lancet"},{"issue":"2","key":"10.1016\/j.esmoop.2025.105049_bib2","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.annonc.2022.10.506","article-title":"Biliary tract cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up","volume":"34","author":"Vogel","year":"2023","journal-title":"Ann Oncol"},{"issue":"9","key":"10.1016\/j.esmoop.2025.105049_bib3","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1001\/jamasurg.2020.1973","article-title":"Very early recurrence after liver resection for intrahepatic cholangiocarcinoma: considering alternative treatment approaches","volume":"155","author":"Tsilimigras","year":"2020","journal-title":"JAMA Surg"},{"issue":"6","key":"10.1016\/j.esmoop.2025.105049_bib4","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1001\/jamasurg.2013.5137","article-title":"Treatment and prognosis for patients with intrahepatic cholangiocarcinoma: systematic review and meta-analysis","volume":"149","author":"Mavros","year":"2014","journal-title":"JAMA Surg"},{"issue":"9","key":"10.1016\/j.esmoop.2025.105049_bib5","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1038\/ng.3375","article-title":"Genomic spectra of biliary tract cancer","volume":"47","author":"Nakamura","year":"2015","journal-title":"Nat Genet"},{"issue":"3","key":"10.1016\/j.esmoop.2025.105049_bib6","doi-asserted-by":"crossref","DOI":"10.1016\/j.esmoop.2022.100505","article-title":"Role of molecular genetics in the clinical management of cholangiocarcinoma","volume":"7","author":"Normanno","year":"2022","journal-title":"ESMO Open"},{"issue":"11","key":"10.1016\/j.esmoop.2025.105049_bib7","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1016\/j.annonc.2020.07.014","article-title":"Recommendations for the use of next-generation sequencing (NGS) for patients with metastatic cancers: a report from the ESMO Precision Medicine Working Group","volume":"31","author":"Mosele","year":"2020","journal-title":"Ann Oncol"},{"key":"10.1016\/j.esmoop.2025.105049_bib8","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.semcdb.2015.04.009","article-title":"Claudins: gatekeepers of lung epithelial function","volume":"42","author":"Schlingmann","year":"2015","journal-title":"Semin Cell Dev Biol"},{"issue":"23","key":"10.1016\/j.esmoop.2025.105049_bib9","doi-asserted-by":"crossref","first-page":"7624","DOI":"10.1158\/1078-0432.CCR-08-1547","article-title":"Claudin-18 splice variant 2 is a pan-cancer target suitable for therapeutic antibody development","volume":"14","author":"Sahin","year":"2008","journal-title":"Clin Cancer Res"},{"issue":"10389","key":"10.1016\/j.esmoop.2025.105049_bib10","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1016\/S0140-6736(23)00620-7","article-title":"Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): a multicentre, randomised, double-blind, phase 3 trial","volume":"401","author":"Shitara","year":"2023","journal-title":"Lancet"},{"issue":"8","key":"10.1016\/j.esmoop.2025.105049_bib11","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.1038\/s41591-023-02465-7","article-title":"Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial","volume":"29","author":"Shah","year":"2023","journal-title":"Nat Med"},{"issue":"10389","key":"10.1016\/j.esmoop.2025.105049_bib12","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1016\/S0140-6736(23)00732-8","article-title":"Claudin-18.2 targeting by zolbetuximab: results of SPOTLIGHT in perspective","volume":"401","author":"van Laarhoven","year":"2023","journal-title":"Lancet"},{"issue":"1","key":"10.1016\/j.esmoop.2025.105049_bib13","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/s00428-011-1092-z","article-title":"Claudin-18 in biliary neoplasms. Its significance in the classification of intrahepatic cholangiocarcinoma","volume":"459","author":"Shinozaki","year":"2011","journal-title":"Virchows Arch"},{"issue":"4","key":"10.1016\/j.esmoop.2025.105049_bib14","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1111\/his.15407","article-title":"Expression of claudin-18.2 in cholangiocarcinoma: a comprehensive immunohistochemical analysis from a German tertiary centre","volume":"86","author":"Kinzler","year":"2024","journal-title":"Histopathology"},{"key":"10.1016\/j.esmoop.2025.105049_bib15","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.ejca.2022.02.013","article-title":"Prognostic impact of FGFR2\/3 alterations in patients with biliary tract cancers receiving systemic chemotherapy: the BITCOIN study","volume":"166","author":"Rizzato","year":"2022","journal-title":"Eur J Cancer"},{"key":"10.1016\/j.esmoop.2025.105049_bib16","series-title":"Digestive System Tumours","article-title":"WHO Classification of Tumours Editorial Board","volume":"1","author":"Nagtegaal","year":"2019"},{"issue":"5","key":"10.1016\/j.esmoop.2025.105049_bib17","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1007\/s00428-019-02624-7","article-title":"Expression of the potential therapeutic target claudin-18.2 is frequently decreased in gastric cancer: results from a large Caucasian cohort study","volume":"475","author":"Dottermusch","year":"2019","journal-title":"Virchows Arch"},{"issue":"11","key":"10.1016\/j.esmoop.2025.105049_bib18","doi-asserted-by":"crossref","DOI":"10.1016\/j.modpat.2024.100589","article-title":"Claudin-18.2 immunohistochemical evaluation in gastric and gastroesophageal junction adenocarcinomas to direct targeted therapy: a practical approach","volume":"37","author":"Fassan","year":"2024","journal-title":"Mod Pathol"},{"issue":"1","key":"10.1016\/j.esmoop.2025.105049_bib19","article-title":"Heterogeneity of claudin 18.2 expression in metastatic gastric cancer","volume":"14","author":"Choi","year":"2024","journal-title":"Sci Rep"},{"issue":"1","key":"10.1016\/j.esmoop.2025.105049_bib20","article-title":"Clinicopathologic features and prognostic value of claudin 18.2 overexpression in patients with resectable gastric cancer","volume":"13","author":"Kim","year":"2023","journal-title":"Sci Rep"},{"issue":"10391","key":"10.1016\/j.esmoop.2025.105049_bib21","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1016\/S0140-6736(23)00727-4","article-title":"Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer (KEYNOTE-966): a randomised, double-blind, placebo-controlled, phase 3 trial","volume":"401","author":"Kelley","year":"2023","journal-title":"Lancet"},{"issue":"8","key":"10.1016\/j.esmoop.2025.105049_bib22","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1016\/S2468-1253(24)00095-5","article-title":"Durvalumab or placebo plus gemcitabine and cisplatin in participants with advanced biliary tract cancer (TOPAZ-1): updated overall survival from a randomised phase 3 study","volume":"9","author":"Oh","year":"2024","journal-title":"Lancet Gastroenterol Hepatol"},{"issue":"9","key":"10.1016\/j.esmoop.2025.105049_bib23","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/s41575-020-0310-z","article-title":"Cholangiocarcinoma 2020: the next horizon in mechanisms and management","volume":"17","author":"Banales","year":"2020","journal-title":"Nat Rev Gastroenterol Hepatol"},{"issue":"2","key":"10.1016\/j.esmoop.2025.105049_bib24","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1002\/jhbp.154","article-title":"Pathogenesis and classification of intrahepatic cholangiocarcinoma: different characters of perihilar large duct type versus peripheral small duct type","volume":"22","author":"Aishima","year":"2015","journal-title":"J Hepatobiliary Pancreat Sci"},{"issue":"suppl 1","key":"10.1016\/j.esmoop.2025.105049_bib25","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1111\/liv.14093","article-title":"Anatomical, histomorphological and molecular classification of cholangiocarcinoma","volume":"39","author":"Kendall","year":"2019","journal-title":"Liver Int"},{"issue":"12","key":"10.1016\/j.esmoop.2025.105049_bib26","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.1097\/PAS.0000000000001583","article-title":"Claudin-18 as a marker for identifying the stomach and pancreatobiliary tract as the primary sites of metastatic adenocarcinoma","volume":"44","author":"Li","year":"2020","journal-title":"Am J Surg Pathol"},{"issue":"9","key":"10.1016\/j.esmoop.2025.105049_bib27","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1016\/j.annonc.2021.04.012","article-title":"Practical considerations in screening for genetic alterations in cholangiocarcinoma","volume":"32","author":"Bekaii-Saab","year":"2021","journal-title":"Ann Oncol"},{"key":"10.1016\/j.esmoop.2025.105049_bib28","doi-asserted-by":"crossref","DOI":"10.1016\/j.critrevonc.2023.104224","article-title":"Practical guidelines for molecular testing of cholangiocarcinoma in clinical practice: Italian experts\u2019 position paper","volume":"194","author":"Fassan","year":"2024","journal-title":"Crit Rev Oncol Hematol"},{"issue":"11","key":"10.1016\/j.esmoop.2025.105049_bib29","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.3390\/jpm11111095","article-title":"Association of CLDN18 protein expression with clinicopathological features and prognosis in advanced gastric and gastroesophageal junction adenocarcinomas","volume":"11","author":"Pellino","year":"2021","journal-title":"J Pers Med"},{"issue":"10","key":"10.1016\/j.esmoop.2025.105049_bib30","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1369\/0022155411420569","article-title":"Claudin-18 is an early-stage marker of pancreatic carcinogenesis","volume":"59","author":"Tanaka","year":"2011","journal-title":"J Histochem Cytochem"},{"key":"10.1016\/j.esmoop.2025.105049_bib31","doi-asserted-by":"crossref","DOI":"10.1016\/j.annonc.2021.05.169","article-title":"P-114 Claudin 18 isoform expression in gastric adenocarcinoma and pancreatic adenocarcinoma","volume":"32","author":"Saito","year":"2021","journal-title":"Ann Oncol"}],"container-title":["ESMO Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2059702925009184?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2059702925009184?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T07:45:29Z","timestamp":1757576729000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2059702925009184"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5]]},"references-count":31,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,5]]}},"alternative-id":["S2059702925009184"],"URL":"https:\/\/doi.org\/10.1016\/j.esmoop.2025.105049","relation":{},"ISSN":["2059-7029"],"issn-type":[{"value":"2059-7029","type":"print"}],"subject":[],"published":{"date-parts":[[2025,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Claudin 18.2: a promising actionable target in biliary tract cancers","name":"articletitle","label":"Article Title"},{"value":"ESMO Open","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.esmoop.2025.105049","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Author(s). Published by Elsevier Ltd on behalf of European Society for Medical Oncology.","name":"copyright","label":"Copyright"}],"article-number":"105049"}}