ADA and cholangiocarcinoma: Some studies [10, 20] demonstrated that metformin exerted antitumoral effects by (1) inhibiting adenosine deaminase that converts AMP into IMP, resulting in AMP accumulation with a subsequent activation of AMPK; (2) activating AMPK that plays a role in cellular energy homeostasis [21]; (3) blocking the mitochondrial respiratory chain complex (NADH dehydrogenase) that impairs ATP synthesis and increasing the AMP/ATP ratio [15]; and (4) metformin targeting the AMPK/mTORC1 pathway in cholangiocarcinoma cells [9, 22].