{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T18:35:54Z","timestamp":1793730954057,"version":"4.6.1"},"reference-count":156,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,3,31]],"date-time":"2022-03-31T00:00:00Z","timestamp":1648684800000},"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>Perihilar cholangiocarcinoma (pCCA) is the anatomical sub-group of biliary tract cancer (BTC) arising between the second-order intrahepatic bile ducts and the cystic duct. Together with distal and intrahepatic cholangiocarcinoma (dCCA and iCCA; originating distal to, and proximal to this, respectively), gallbladder cancer (GBC) and ampulla of Vater carcinoma (AVC), these clinicopathologically and molecularly distinct entities comprise biliary tract cancer (BTC). Most pCCAs are unresectable at diagnosis, and for those with resectable disease, surgery is extensive, and recurrence is common. Therefore, the majority of patients with pCCA will require systemic treatment for advanced disease. The prognosis with cytotoxic chemotherapy remains poor, driving interest in therapies targeted to the molecular nature of a given patient\u2019s cancer. In recent years, the search for efficacious targeted therapies has been fuelled both by whole-genome and epigenomic studies, looking to uncover the molecular landscape of CCA, and by specifically testing for aberrations where established therapies exist in other indications. This review aims to provide a focus on the current molecular characterisation of pCCA, targeted therapies applicable to pCCA, and future directions in applying personalised medicine to this difficult-to-treat malignancy.<\/jats:p>","DOI":"10.3390\/cancers14071789","type":"journal-article","created":{"date-parts":[[2022,3,31]],"date-time":"2022-03-31T21:33:03Z","timestamp":1648762383000},"page":"1789","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Targeted Therapies for Perihilar Cholangiocarcinoma"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8396-3328","authenticated-orcid":false,"given":"Simon","family":"Gray","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, The Christie NHS Foundation Trust, Wilmslow Rd, Manchester M20 4BX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Lamarca","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, The Christie NHS Foundation Trust, Wilmslow Rd, Manchester M20 4BX, UK"},{"name":"Division of Cancer Sciences, University of Manchester, Oxford Rd, Manchester M13 9PL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8289-7741","authenticated-orcid":false,"given":"Julien","family":"Edeline","sequence":"additional","affiliation":[{"name":"Centre Eug\u00e8ne Marquis, Av. de la Bataille Flandres Dunkerque-CS 44229, CEDEX, 35042 Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7290-1823","authenticated-orcid":false,"given":"Heinz-Josef","family":"Kl\u00fcmpen","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Amsterdam University Medical Center, P.O. Box 7057, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Hubner","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, The Christie NHS Foundation Trust, Wilmslow Rd, Manchester M20 4BX, UK"},{"name":"Division of Cancer Sciences, University of Manchester, Oxford Rd, Manchester M13 9PL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2272-3678","authenticated-orcid":false,"given":"Mair\u00e9ad G.","family":"McNamara","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, The Christie NHS Foundation Trust, Wilmslow Rd, Manchester M20 4BX, UK"},{"name":"Division of Cancer Sciences, University of Manchester, Oxford Rd, Manchester M13 9PL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1999-0863","authenticated-orcid":false,"given":"Juan W.","family":"Valle","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, The Christie NHS Foundation Trust, Wilmslow Rd, Manchester M20 4BX, UK"},{"name":"Division of Cancer Sciences, University of Manchester, Oxford Rd, Manchester M13 9PL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,31]]},"reference":[{"key":"ref_1","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"},{"key":"ref_2","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. 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