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Cholangiocarcinoma (CCA) is the most common biliary malignancy, and has a poor prognosis. The median overall survival with the standard-of-care chemotherapy (Gemcitabine and cisplatin) in patients with advanced-stage CCA is less than one year. The limited efficacy of chemotherapy or targeted therapy remains a major obstacle to improving survival. The mechanisms involved in drug resistance are complex. Research efforts focusing on the distinct molecular mechanisms underlying drug resistance should prompt the development of treatment stra