{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T09:26:53Z","timestamp":1780392413923,"version":"3.54.1"},"reference-count":138,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,8,6]],"date-time":"2020-08-06T00:00:00Z","timestamp":1596672000000},"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>Biliary tract cancers (BTCs) are a group of rare cancers that account for up to 3\u20135% of cancer patients worldwide. BTCs include cholangiocarcinoma (CCA), gallbladder cancer (GBC), and ampulla of Vater cancer (AVC). They are frequently diagnosed at an advanced stage when the disease is often found disseminated. A late diagnosis highly compromises surgery, the only potentially curative option. Current treatment regimens include a combination of chemotherapeutic drugs gemcitabine with cisplatin that have a limited efficiency since more than 50% of patients relapse in the first year. More recently, an inhibitor of fibroblast growth factor receptor 2 (FGFR2) was approved as a second-line treatment, based on the promising results from the NCT02924376 clinical trial. However, novel secondary treatment options are urgently needed. Recent molecular characterization of CCA and GBC highlighted the molecular heterogeneity, etiology, and epidemiology in BTC development and lead to the classification of the extrahepatic CCA into four types: metabolic, proliferating, mesenchymal, and immune type. Differences in the immune infiltration and tumor microenvironment (TME) have been described as well, showing that only a small subset of BTCs could be classified as an immune \u201chot\u201d and targeted with the immunotherapeutic drugs. This recent evidence has opened a way to new clinical trials for BTCs, and new drug approvals are highly expected by the medical community.<\/jats:p>","DOI":"10.3390\/cancers12082190","type":"journal-article","created":{"date-parts":[[2020,8,6]],"date-time":"2020-08-06T09:41:21Z","timestamp":1596706881000},"page":"2190","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Molecular and Immunological Characterization of Biliary Tract Cancers: A Paradigm Shift Towards a Personalized Medicine"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5401-4024","authenticated-orcid":false,"given":"Ines","family":"Malenica","sequence":"first","affiliation":[{"name":"Hepatobiliary Immunopathology Unit, Humanitas Clinical and Research Center-IRCCS, 20090 Pieve Emanuele, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0296-7648","authenticated-orcid":false,"given":"Matteo","family":"Donadon","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and General Surgery, Humanitas Clinical and Research Center-IRCCS, 20089 Rozzano, Italy"},{"name":"Department of Biomedical Science, Humanitas University, 20089 Rozzano, 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 Science, Humanitas University, 20089 Rozzano, Italy"},{"name":"Internal Medicine and Hepatology Unit, Humanitas Clinical and Research Center-IRCCS, 20089 Rozzano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2623","DOI":"10.2147\/CMAR.S157092","article-title":"Biliary tract cancers: Current knowledge, clinical candidates and future challenges","volume":"11","author":"Tariq","year":"2019","journal-title":"Cancer Manag. 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