{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T23:16:29Z","timestamp":1780960589012,"version":"3.54.1"},"reference-count":111,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T00:00:00Z","timestamp":1697414400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Primary tumor resection and liver transplantation are the only curative treatment options for the management of cholangiocarcinoma (CCA). However, for patients with advanced or metastatic disease, palliative systemic therapy remains the only treatment option. The development of targeted therapeutics has begun to shift the treatment paradigm in CCA. Targets of interest in CCA include mutated isocitrate dehydrogenase-1 (mIDH-1), human epidermal growth factor receptor 2 (HER2) overexpression\/amplification, and fibroblast growth factor receptor 2 (FGFR2) fusion, in addition to less frequently observed targets such as BRAF V600E, deficient mismatch repair\/high microsatellite instability (dMMR\/MSI-H), and high tumor mutation burden (TMB-H). These targets are observed in varying frequency among patients with intrahepatic CCA and extrahepatic CCA. Multiple novel therapies have been developed to exploit each of these targets, with some having received United States Food and Drug Administration approval for use in the second-line setting. In the current review, we discuss targets of interest in CCA and summarize current evidence evaluating available therapies directed at these targets.<\/jats:p>","DOI":"10.3390\/life13102066","type":"journal-article","created":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T10:06:36Z","timestamp":1697450796000},"page":"2066","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Targeted Therapies in Advanced Cholangiocarcinoma"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1266-7393","authenticated-orcid":false,"given":"Michael H.","family":"Storandt","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter C.","family":"Kurniali","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Medical Oncology, Sanford Cancer Center, Bismarck, ND 58501, USA"},{"name":"Department of Internal Medicine, Division of Hematology\/Oncology, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Mahipal","sequence":"additional","affiliation":[{"name":"Department of Oncology, University Hospitals Seidman Cancer Center and Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7844-5833","authenticated-orcid":false,"given":"Zhaohui","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1053\/j.gastro.2013.10.013","article-title":"Pathogenesis, Diagnosis, and Management of Cholangiocarcinoma","volume":"145","author":"Rizvi","year":"2013","journal-title":"Gastroenterology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/nrgastro.2016.51","article-title":"Expert Consensus Document: Cholangiocarcinoma: Current Knowledge and Future Perspectives Consensus Statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA)","volume":"13","author":"Banales","year":"2016","journal-title":"Nat. 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