{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T11:55:32Z","timestamp":1790423732181,"version":"4.1.0"},"reference-count":113,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,11,13]],"date-time":"2020-11-13T00:00:00Z","timestamp":1605225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["IG AIRC 2019 \u2013 ID 23408"],"award-info":[{"award-number":["IG AIRC 2019 \u2013 ID 23408"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Most patients with biliary tract cancer (BTC) are diagnosed with advanced disease, relapse rates are high in those undergoing surgery and prognosis remains poor, while the incidence is increasing. Treatment options are limited, and chemotherapy is still the standard of care in both adjuvant and advanced disease setting. In recent years, different subtypes of BTC have been defined depending on the anatomical location and genetic and\/or epigenetic aberrations. Especially for intrahepatic cholangiocarcinoma (iCCA) novel therapeutic targets have been identified, including fibroblast growth factor receptor 2 gene fusions and isocitrate dehydrogenase 1 and 2 mutations, with molecularly targeted agents having shown evidence of activity in this subgroup of patients. Additionally, other pathways are being evaluated in both iCCA and other subtypes of BTC, alongside targeting of the immune microenvironment. The growing knowledge of BTC biology and molecular heterogeneity has paved the way for the development of new therapeutic approaches that will completely change the treatment paradigm for this disease in the near future. This review provides an overview of the molecular heterogeneity of BTC and summarizes new targets and emerging therapies in development. We also discuss resistance mechanisms, open issues, and future perspectives in the management of BTC.<\/jats:p>","DOI":"10.3390\/cancers12113370","type":"journal-article","created":{"date-parts":[[2020,11,13]],"date-time":"2020-11-13T10:32:47Z","timestamp":1605263567000},"page":"3370","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Biliary Tract Cancers: Molecular Heterogeneity and New Treatment Options"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7995-272X","authenticated-orcid":false,"given":"Nicola","family":"Personeni","sequence":"first","affiliation":[{"name":"Medical Oncology and Hematology Unit, Humanitas Cancer Center, Humanitas Clinical and Research Center-IRCCS, 20089 Rozzano (Milan), Italy"},{"name":"Department of Biomedical Sciences, Humanitas University, 20090 Pieve Emanuele (Milan), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0561-7902","authenticated-orcid":false,"given":"Ana","family":"Lleo","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University, 20090 Pieve Emanuele (Milan), Italy"},{"name":"Internal Medicine Center, Humanitas Clinical and Research Center-IRCCS, 20089 Rozzano (Milan), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiziana","family":"Pressiani","sequence":"additional","affiliation":[{"name":"Medical Oncology and Hematology Unit, Humanitas Cancer Center, Humanitas Clinical and Research Center-IRCCS, 20089 Rozzano (Milan), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Colapietro","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University, 20090 Pieve Emanuele (Milan), Italy"},{"name":"Internal Medicine Center, Humanitas Clinical and Research Center-IRCCS, 20089 Rozzano (Milan), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark Robert","family":"Openshaw","sequence":"additional","affiliation":[{"name":"Department of Surgery &amp; Cancer, Imperial College London, Hammersmith Hospital, London W120HS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7623-299X","authenticated-orcid":false,"given":"Chara","family":"Stavraka","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Guy's and St Thomas' NHS Foundation Trust, Great Maze Pond, London SE1 9RT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athanasios","family":"Pouptsis","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, \u201cEuromedica\u201d General Clinic, 54645 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David James","family":"Pinato","sequence":"additional","affiliation":[{"name":"Department of Surgery &amp; Cancer, Imperial College London, Hammersmith Hospital, London W120HS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9957-3615","authenticated-orcid":false,"given":"Lorenza","family":"Rimassa","sequence":"additional","affiliation":[{"name":"Medical Oncology and Hematology Unit, Humanitas Cancer Center, Humanitas Clinical and Research Center-IRCCS, 20089 Rozzano (Milan), Italy"},{"name":"Department of Biomedical Sciences, Humanitas University, 20090 Pieve Emanuele (Milan), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.jaut.2019.03.007","article-title":"The immune milieu of cholangiocarcinoma: From molecular pathogenesis to precision medicine","volume":"100","author":"Rimassa","year":"2019","journal-title":"J. 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