Targeting cellular metabolism in cholangiocarcinoma with dithiazanine iodide

Abstract

Background: Cholangiocarcinoma is a rare, aggressive cancer of the biliary tree which accounts for 10-20% of periampullary cancers. Therapy for cholangiocarcinoma is challenging, as this cancer is extremely resistant to standard chemotherapy regimens which act through the induction of DNA damage. The cholangiocarcinoma microenvironment is relatively hypovascular and as such, is characterized by relative hypoxia and nutrient depletion. We therefore hypothesized that metabolic inhibitors, targeting mitochondrial function might be a useful adjunct for cholangiocarcinoma treatment. We assessed the potential of the previously FDA-approved anti-parasitic compound, Dithiazanine Iodide (CDI), as an anti-cancer drug in in-vitro cell cultures of patient-derived cholangiocarcinoma cell lines and we have shown here that CDI is a strong, targeted mitochondrial inhibitor.