{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T11:47:21Z","timestamp":1782906441785,"version":"3.54.5"},"reference-count":210,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"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>Biliary tract cancers (BTCs) comprise a heterogeneous group of malignancies arising from the biliary tree, including cholangiocarcinomas and gallbladder carcinomas. Although their incidence is rising globally in Western countries, these cancers are rare and most often diagnosed at advanced stages. Their molecular heterogeneity and frequent resistance to therapy further contribute to their dismal prognosis. In recent years, molecular profiling studies have led to a better understanding of BTC biology and have opened new therapeutic opportunities, particularly for patients with advanced or metastatic disease. Alterations in DNA damage repair (DDR) genes have been identified in a substantial proportion of BTC cases, with some cohorts observing frequencies approaching ~70%. These genetic alterations play a critical role in tumorigenesis and disease progression and may contribute to treatment resistance. In this article, we discuss the current knowledge on: (1) the main DDR signaling pathways; (2) the prevalence of DDR gene alterations across BTC subtypes; (3) the potential of DDR gene alterations as prognostic and\/or predictive biomarkers of treatment response; and (4) the latest advances in DDR-based targeted therapies and ongoing clinical trials in BTC.<\/jats:p>","DOI":"10.3390\/cancers18132134","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T10:41:01Z","timestamp":1782902461000},"page":"2134","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prognostic, Predictive, and Clinical Relevance of DNA Damage Repair Alterations in Biliary Tract Cancers"],"prefix":"10.3390","volume":"18","author":[{"given":"Jawad","family":"Tarfouss","sequence":"first","affiliation":[{"name":"Laboratory of Experimental Gastroenterology, Universit\u00e9 Libre de Bruxelles, Route de Lennik 808, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1658-6111","authenticated-orcid":false,"given":"Oier","family":"Azurmendi Senar","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Gastroenterology, Universit\u00e9 Libre de Bruxelles, Route de Lennik 808, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2984-034X","authenticated-orcid":false,"given":"Kosta","family":"Stosic","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Gastroenterology, Universit\u00e9 Libre de Bruxelles, Route de Lennik 808, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurine","family":"Verset","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Gastroenterology, Universit\u00e9 Libre de Bruxelles, Route de Lennik 808, 1070 Brussels, Belgium"},{"name":"Department of Pathology, H\u00f4pital Universitaire de Bruxelles (H.U.B.) Bordet Erasme, Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christelle","family":"Bouchart","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Gastroenterology, Universit\u00e9 Libre de Bruxelles, Route de Lennik 808, 1070 Brussels, Belgium"},{"name":"Department of Radiation Oncology, H\u00f4pital Universitaire de Bruxelles (H.U.B.) Bordet Erasme, Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5362-8764","authenticated-orcid":false,"given":"Julie","family":"Navez","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Gastroenterology, Universit\u00e9 Libre de Bruxelles, Route de Lennik 808, 1070 Brussels, Belgium"},{"name":"Department of Hepato-Biliary-Pancreatic Surgery, H\u00f4pital Universitaire de Bruxelles (H.U.B.) Bordet Erasme, Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Luc","family":"Van Laethem","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Gastroenterology, Universit\u00e9 Libre de Bruxelles, Route de Lennik 808, 1070 Brussels, Belgium"},{"name":"Department of Gastroenterology, Hepatology and Digestive Oncology, Hopital Universitaire de Bruxelles (H.U.B.), Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2886-6650","authenticated-orcid":false,"given":"Anne","family":"Demols","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Gastroenterology, Universit\u00e9 Libre de Bruxelles, Route de Lennik 808, 1070 Brussels, Belgium"},{"name":"Department of Gastroenterology, Hepatology and Digestive Oncology, Hopital Universitaire de Bruxelles (H.U.B.), Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatjana","family":"Arsenijevic","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Gastroenterology, Universit\u00e9 Libre de Bruxelles, Route de Lennik 808, 1070 Brussels, Belgium"},{"name":"Department of Gastroenterology, Hepatology and Digestive Oncology, Hopital Universitaire de Bruxelles (H.U.B.), Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2168","DOI":"10.1016\/S0140-6736(13)61903-0","article-title":"Cholangiocarcinoma","volume":"383","author":"Razumilava","year":"2014","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e25635","DOI":"10.1097\/MD.0000000000025635","article-title":"Analysis of Metastasis and Survival between Extrahepatic and Intrahepatic Cholangiocarcinoma: A Large Population-Based Study","volume":"100","author":"Liao","year":"2021","journal-title":"Medicine"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1097\/00000658-199610000-00005","article-title":"Cholangiocarcinoma: A Spectrum of Intrahepatic, Perihilar, and Distal Tumors","volume":"224","author":"Nakeeb","year":"1996","journal-title":"Ann. 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