{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T14:20:53Z","timestamp":1766067653543,"version":"build-2065373602"},"reference-count":87,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cholangiocarcinoma (CCA) is a malignant neoplasm arising in the epithelium of the biliary tract. It represents the second most common primary liver cancer in the world, after hepatocellular carcinoma, and it constitutes 10\u201315% of hepatobiliary neoplasms and 3% of all gastrointestinal tumors. As in other types of cancers, recent studies have revealed genetic alterations underlying the establishment and progression of CCA. The most frequently involved genes are APC, ARID1A, AXIN1, BAP1, EGFR, FGFRs, IDH1\/2, RAS, SMAD4, and TP53. Actionable targets include alterations of FGFRs, IDH1\/2, BRAF, NTRK, and HER2. \u201cPrecision oncology\u201d is emerging as a promising approach for CCA, and it is possible to inhibit the altered function of these genes with molecularly oriented drugs (pemigatinib, ivosidenib, vemurafenib, larotrectinib, and trastuzumab). In this review, we provide an overview of new biologic drugs (their structures, mechanisms of action, and toxicities) to treat metastatic CCA, providing readers with panoramic information on the trajectory from \u201cold\u201d chemotherapies to \u201cnew\u201d target-oriented drugs.<\/jats:p>","DOI":"10.3390\/ijms232315124","type":"journal-article","created":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T01:44:46Z","timestamp":1669945486000},"page":"15124","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Evolution of Treatment in Advanced Cholangiocarcinoma: Old and New towards Precision Oncology"],"prefix":"10.3390","volume":"23","author":[{"given":"Maurizio","family":"Capuozzo","sequence":"first","affiliation":[{"name":"Coordinamento Farmaceutico, ASL-Naples-3, 80056 Ercolano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariachiara","family":"Santorsola","sequence":"additional","affiliation":[{"name":"Istituto Nazionale Tumori di Napoli, IRCCS \u201cG. Pascale\u201d, Via M. Semmola, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Loris","family":"Landi","sequence":"additional","affiliation":[{"name":"Sanitary District, Ds. 58 ASL-Naples-3, 80056 Ercolano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6601-3221","authenticated-orcid":false,"given":"Vincenza","family":"Granata","sequence":"additional","affiliation":[{"name":"Istituto Nazionale Tumori di Napoli, IRCCS \u201cG. Pascale\u201d, Via M. Semmola, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8158-7509","authenticated-orcid":false,"given":"Francesco","family":"Perri","sequence":"additional","affiliation":[{"name":"Istituto Nazionale Tumori di Napoli, IRCCS \u201cG. Pascale\u201d, Via M. Semmola, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Venere","family":"Celotto","sequence":"additional","affiliation":[{"name":"Coordinamento Farmaceutico, ASL-Naples-3, 80056 Ercolano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7154-1328","authenticated-orcid":false,"given":"Oreste","family":"Gualillo","sequence":"additional","affiliation":[{"name":"SERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigaci\u00f3n Sanitaria de Santiago), NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Research Laboratory 9, Santiago University Clinical Hospital, 15706 Santiago de Compostela, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guglielmo","family":"Nasti","sequence":"additional","affiliation":[{"name":"Istituto Nazionale Tumori di Napoli, IRCCS \u201cG. Pascale\u201d, Via M. Semmola, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2901-3855","authenticated-orcid":false,"given":"Alessandro","family":"Ottaiano","sequence":"additional","affiliation":[{"name":"Istituto Nazionale Tumori di Napoli, IRCCS \u201cG. Pascale\u201d, Via M. Semmola, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100335","DOI":"10.1016\/j.ctarc.2021.100335","article-title":"First-line Chemotherapy in Advanced Biliary Tract Cancer Ten Years After the ABC-02 Trial: \u201cAnd Yet It Moves!\u201d","volume":"27","author":"Rizzo","year":"2021","journal-title":"Cancer Treat. Res. 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