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Several conditions are known to be major risk factors for cancer in the biliary tract or gallbladder, including primary sclerosing cholangitis, liver fluke infection, pancreaticobiliary maljunction, and chemical exposure in proof\u2010printing workers. Abnormalities in various signaling cascades, molecules, and genetic mutations are involved in the pathogenesis of<jats:styled-content style=\"fixed-case\">CCA<\/jats:styled-content>.<jats:styled-content style=\"fixed-case\">CCA<\/jats:styled-content>is characterized by a series of highly recurrent mutations in genes, including<jats:italic><jats:styled-content style=\"fixed-case\">KRAS<\/jats:styled-content><\/jats:italic>,<jats:italic><jats:styled-content style=\"fixed-case\">BRF<\/jats:styled-content><\/jats:italic>,<jats:italic><jats:styled-content style=\"fixed-case\">TP53<\/jats:styled-content><\/jats:italic>,<jats:italic><jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>mad<\/jats:italic>, and<jats:italic>p16<jats:sup>INK4a<\/jats:sup><\/jats:italic>. Cytokines that are affected by inflammatory environmental conditions, such as interleukin\u20106 (<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106), transforming growth factor\u2010\u03b2 (<jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\u2010\u03b2), tumor necrosis factor\u2010\u03b1 (<jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u2010\u03b1), and platelet\u2010derived growth factor (<jats:styled-content style=\"fixed-case\">PDGF<\/jats:styled-content>), play an important role in cancer pathogenesis. Prominent signaling pathways important in carcinogenesis include<jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\u2010\u03b2\/<jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>mad,<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106\/<jats:styled-content style=\"fixed-case\">STAT<\/jats:styled-content>\u20103,<jats:styled-content style=\"fixed-case\">PI3K<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">AKT<\/jats:styled-content>, Wnt,<jats:styled-content style=\"fixed-case\">RAF<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">MEK<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">MAPK<\/jats:styled-content>, and<jats:styled-content style=\"fixed-case\">N<\/jats:styled-content>otch. Additionally, some micro<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>s regulate targets in critical pathways of<jats:styled-content style=\"fixed-case\">CCA<\/jats:styled-content>development and progression. This review article provides the understanding of the genetic and epigenetic mechanism(s) of carcinogenesis in<jats:styled-content style=\"fixed-case\">CCA,<\/jats:styled-content>which leads to the development of new therapeutic targets for the prevention and treatment of this devastating cancer.<\/jats:p>","DOI":"10.1002\/jhbp.126","type":"journal-article","created":{"date-parts":[[2014,6,3]],"date-time":"2014-06-03T23:52:58Z","timestamp":1401839578000},"page":"754-760","source":"Crossref","is-referenced-by-count":70,"title":["Molecular mechanism of cholangiocarcinoma carcinogenesis"],"prefix":"10.1002","volume":"21","author":[{"given":"Kosei","family":"Maemura","sequence":"first","affiliation":[{"name":"Department of Digestive Surgery, Breast and Thyroid Surgery Kagoshima University Graduate School of Medical and Dental Sciences Kagoshima 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