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Research on dCCA is limited by the scarcity of reliable patient-derived preclinical tumor models. This study established a novel human distal cholangiocarcinoma cell line, CBC3T-3, and systematically characterized its biological properties, genomic features, and potential for clinical application. This cell line was extracted from postoperative distal cholangiocarcinoma tumor from a 54-year-old male patient. It was stably passaged (&gt;\u200950 generations) through primary culture and condition optimization, preserving the same pathology as that of the primary tumor. Whole-exome sequencing (WES) confirmed somatic mutations, tumor mutation burden, single-sample clonal structure, driver genes, and drug resistance genes in CBC3T-3 cells, revealing their genomic characteristics. Functional assays demonstrated that CBC3T-3 cells exhibit strong capabilities for proliferation, migration, and invasion in vitro. In a subcutaneous xenograft model in immunodeficient mice, palpable tumor nodules developed within 4 weeks, reflecting the clinical characteristics of rapidly progressive disease. Drug sensitivity analysis revealed that, compared with TFK-1 cells, CBC3T-3 cells presented significantly greater responses to paclitaxel, gemcitabine, and oxaliplatin but relatively poor responses to 5-FU and cisplatin. The integration of drug resistance gene findings from WES suggests that\n                    <jats:italic>TP53<\/jats:italic>\n                    missense mutations may mediate primary resistance to cisplatin. The establishment of the CBC3T-3 cell line enhances the research toolkit for dCCA. Its genomic characteristics and functional plasticity provide a reliable preclinical tumor model for developing precision therapies and investigating drug resistance mechanisms.\n                  <\/jats:p>","DOI":"10.1007\/s13577-026-01369-1","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T19:19:48Z","timestamp":1774984788000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["CBC3T-3: a novel patient-derived cisplatin-resistant distal cholangiocarcinoma cell line harboring multiple TP53 missense mutations"],"prefix":"10.1007","volume":"39","author":[{"given":"Jiahui","family":"Xi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingzhen","family":"Bai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruyang","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chongfei","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruoshui","family":"An","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Long","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haidong","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liang","family":"Tian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinyu","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ningzu","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiang","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leiqing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zihe","family":"Dong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Yue","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanyan","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongtian","family":"Bai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenbo","family":"Meng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,3,31]]},"reference":[{"key":"1369_CR1","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1038\/s41575-020-0310-z","volume":"17","author":"JM Banales","year":"2020","unstructured":"Banales JM, Marin JJG, Lamarca A, et al. 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