Bile acids in liver and gastrointestinal cancer
María J. Monte, Laura Fàbrega, Marta R. Romero, Álvaro G. Temprano, Neil Kaplowitz, Carmen García‐Ruiz, José J.G. Marı́n, José C. Fernández‐Checa
Abstract
Bile acids (BAs) are cholesterol-derived metabolites synthesized by hepatocytes and secreted in bile to follow an inter-organ transit to the intestine, where they facilitate fat digestion and the absorption of lipids and liposoluble vitamins. Traditionally considered mere end products of cholesterol catabolism, they are now acknowledged to play intricate roles in regulating intermediary metabolism by controlling the expression of crucial genes. Additionally, they exert a significant impact on inflammation, cytotoxicity, and carcinogenesis. Moreover, BAs have a critical impact on the crosstalk between gut microbiota and host physiology, which affects the progression of liver and gastrointestinal cancers. Clinical data and results from studies of animal models support the involvement of BAs in the development of hepatocellular carcinoma, cholangiocarcinoma, colorectal adenocarcinoma, and pancreatic cancer. On the other hand, BAs and their derivatives have been proposed as pharmacological tools in strategies to restore abnormal hepatobiliary function and target cytostatic agents to cancers of the enterohepatic circuit. In the present review, we summarize basic concepts of BA physiology and regulation, as well as new advances in this expanding field of renewed interest for cancer biology, lending further support for the key role of BAs in liver and gastrointestinal cancer.