Cholangiocarcinoma (CCA) encompasses a group of malignancies that can arise at any point in the biliary tree. Although considered a rare cancer, the incidence of CCA is increasing globally. The silent and asymptomatic nature of these tumors, particularly in their early stages, in combination with their high aggressiveness, intra- and intertumor heterogeneity, and chemoresistance, significantly compromises the efficacy of current therapeutic options, contributing to a dismal prognosis. During the last few years, increasing efforts have been made to unveil the etiologies and pathogenesis of these tumors and to develop more effective therapies. In this review, we summarize current findings in the field of CCA, mainly focusing on the mechanisms of pathogenesis, cells of origin, genomic and epigenetic abnormalities, molecular alterations, chemoresistance, and therapies. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease, Volume 16 is January 25, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
Activation of FXR inhibits, whereas TGR5 activation may promote, CCA progression by regulating proliferation, migration and mitochondrial energy metabolism. Modulation of FXR or TGR5 activities may represent potential therapeutic strategies for CCA.
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