{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T16:28:27Z","timestamp":1777912107423,"version":"3.51.4"},"reference-count":287,"publisher":"Walter de Gruyter GmbH","issue":"2","license":[{"start":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T00:00:00Z","timestamp":1772409600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82460568"],"award-info":[{"award-number":["82460568"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the Key Project of Science and Technology of Gansu Province\u00a0\u2013 International Cooperation Project","award":["25ZDWA009"],"award-info":[{"award-number":["25ZDWA009"]}]},{"name":"Gansu Province Joint Research Fund","award":["25JRRA1261"],"award-info":[{"award-number":["25JRRA1261"]}]},{"name":"Lanzhou City Chengguan District Science and Technology Bureau Science Support Special Project","award":["2025-zc-18"],"award-info":[{"award-number":["2025-zc-18"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Cholangiocarcinoma (CCA) consists of a class of malignant tumors of the biliary system, with a rising incidence and carries a poor prognosis. Developing reliable animal models of CCA is crucial to elucidate the pathogenesis, identify novel therapeutic targets, and assess treatment efficacy. Among these models, the\n                    <jats:italic>in situ<\/jats:italic>\n                    primary cholangiocarcinoma model which closely mimics clinical reality, serves as a robust tool for evaluating drug efficacy, simulating tumor progression characteristics, and facilitates immunotherapy strategies. Although\n                    <jats:italic>in situ<\/jats:italic>\n                    primary CCA models have been utilized in preclinical research, they have inherent limitations that warrant attention and further refinement. This review article highlights the status of the most relevant experimental animal models in preclinical CCA studies. It further delineates the differences in the development of intrahepatic and extrahepatic bile ducts that influence CCA model construction. In addition, we review the advancements, strengths and weaknesses of CCA organoids, primary intrahepatic and extrahepatic CCA models, and examine the pivotal role of bile duct inflammation and biliary fibrosis in creating the invasive cancer models. We emphasize the innovative application and immense potential of single-cell sequencing technology in studying cancer models. Additionally, this article summarizes the progress of CCA-targeted therapies and associated clinical trials which offered relevant insights. With a comprehensive review of\n                    <jats:italic>in situ<\/jats:italic>\n                    primary CCA models, we aim to provide suggestions and recommendation for future development of more advanced and clinically relevant research in constructing CCA models.\n                  <\/jats:p>","DOI":"10.1515\/mr-2025-0081","type":"journal-article","created":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T07:59:57Z","timestamp":1772351997000},"page":"91-119","source":"Crossref","is-referenced-by-count":0,"title":["How to efficiently establish animal models of cholangiocarcinoma: challenges and inspiration"],"prefix":"10.1515","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9257-4786","authenticated-orcid":false,"given":"Ruiqiang","family":"Gou","sequence":"first","affiliation":[{"name":"The First Clinical Medical College , Lanzhou University , Lanzhou , Gansu , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Yue","sequence":"additional","affiliation":[{"name":"117741 General Surgery Department of the First Hospital of Lanzhou University , Lanzhou , Gansu , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Lanzhou University , Lanzhou , Gansu , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinyu","family":"Zhao","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College , Lanzhou University , Lanzhou , Gansu , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunfei","family":"Huang","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College , Lanzhou University , Lanzhou , Gansu , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kiyohito","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology , Kyoto Second Red Cross Hospital , Kyoto , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng F","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery , James Cook University Hospital , Midlands , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rungsun","family":"Rerknimitr","sequence":"additional","affiliation":[{"name":"The Center for Innovation and Endoscopy in Gastrointestinal Oncology of Chulalongkorn University , Bangkok , Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jong H","family":"Moon","sequence":"additional","affiliation":[{"name":"Deparment of Internal Medicine , SoonChunHyang University Bucheon Hospital , Bucheon , Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tan T","family":"Cheung","sequence":"additional","affiliation":[{"name":"Department of Surgery , The University of Hong Kong , Hong Kong , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5291-0853","authenticated-orcid":false,"given":"Christian","family":"Waydhas","sequence":"additional","affiliation":[{"name":"Department of Trauma Surgery , Essen University Hospital , Essen D-45121 , Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Azumi","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology , Hamamatsu Medical Center , Hamamatsu , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanyan","family":"Lin","sequence":"additional","affiliation":[{"name":"117741 General Surgery Department of the First Hospital of Lanzhou University , Lanzhou , Gansu , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emmanuel","family":"Melloul","sequence":"additional","affiliation":[{"name":"Department of Visceral Surgery , University Hospital of Lausanne , Lausanne , Switzerland , Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans","family":"Schlitt","sequence":"additional","affiliation":[{"name":"Regensburg University Hospital Center Surgery Department , Regensburg 93053 , Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Fung","sequence":"additional","affiliation":[{"name":"Institute of Transplantation, Department of Surgery , University of Chicago , Chicago , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph W","family":"Leung","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology , University of California, Davis Medical Center and Sacramento Veterans Affairs Medical Center , Sacramento , 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