{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T02:56:03Z","timestamp":1792119363594,"version":"4.4.0"},"reference-count":103,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2023,7,20]],"date-time":"2023-07-20T00:00:00Z","timestamp":1689811200000},"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>To overcome the poor prognosis of cholangiocarcinoma (CCA), highly targeted therapies, such as antibody-drug conjugates (ADCs), photodynamic therapy (PDT) with\/without systemic chemotherapy, and experimental photoimmunotherapy (PIT), have been developed. Three preclinical trials have investigated the use of ADCs targeting specific antigens, namely HER2, MUC1, and glypican-1 (GPC1), for CCA. Trastuzumab emtansine demonstrated higher antiproliferative activity in CCA cells expressing higher levels of HER2. Similarly, \u201cstaphylococcal enterotoxin A-MUC1 antibody\u201d and \u201canti-GPC1 antibody-monomethyl auristatin F\u201d conjugates showed anticancer activity. PDT is effective in areas where appropriate photosensitizers and light coexist. Its mechanism involves photosensitizer excitation and subsequent reactive oxygen species production in cancer cells upon irradiation. Hematoporphyrin derivatives, temoporfin, phthalocyanine-4, talaporfin, and chlorine e6 derivatives have mainly been used clinically and preclinically in bile duct cancer. Currently, new forms of photosensitizers with nanotechnology and novel irradiation catheters are being developed. PIT is the most novel anti-cancer therapy developed in 2011 that selectively kills targeted cancer cells using a unique photosensitizer called \u201cIR700\u201d conjugated with an antibody specific for cancer cells. PIT is currently in the early stages of development for identifying appropriate CCA cell targets and irradiation devices. Future human and artificial intelligence collaboration has potential for overcoming challenges related to identifying universal CCA cell targets. This could pave the way for highly targeted therapies for CCA, such as ADC, PDT, and PIT.<\/jats:p>","DOI":"10.3390\/cancers15143686","type":"journal-article","created":{"date-parts":[[2023,7,20]],"date-time":"2023-07-20T04:27:13Z","timestamp":1689827233000},"page":"3686","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Promising Highly Targeted Therapies for Cholangiocarcinoma: A Review and Future Perspectives"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0265-6068","authenticated-orcid":false,"given":"Masaki","family":"Kuwatani","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Hokkaido University Hospital, North 14, West 5, Kita-ku, Sapporo 060-8648, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoya","family":"Sakamoto","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Hokkaido University Hospital, North 14, West 5, Kita-ku, Sapporo 060-8648, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1002\/(SICI)1097-0029(19970915)38:6<552::AID-JEMT2>3.0.CO;2-H","article-title":"Microstructure and development of the normal and pathologic biliary tract in humans, including blood supply","volume":"38","author":"Nakanuma","year":"1997","journal-title":"Microsc. 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