Abstract Hepatocellular carcinoma (HCC) is the predominant malignant liver tumor, characterized by high morbidity, mortality and rapid progression, and it ranks among the leading causes of cancer-related fatalities worldwide. Its treatment is facing the severe challenge of resistance to targeted drugs and immunotherapy. Bile acids (BAs) are products of cholesterol metabolism, not only regulate lipid digestion and absorption, but also influence the development of HCC by modulating inflammation and metabolism. Dysregulation of BAs metabolism is closely linked to resistance against targeted therapies and immunotherapies. BAs reduce the efficacy of targeted drugs by influencing enzymes involved in drug metabolism and drug efflux transporters, moreover, BAs also lead to immunotherapeutic resistance by regulating the formation of the immunosuppressive tumor microenvironment (TME). Therefore, regulating BAs metabolism has the potential to overcome drug resistance of targeted therapy and immunotherapy, which could be a promising treatment strategy. This review not only summarizes the roles of BAs metabolism in HCC development and drug resistance, but also further explores the rationality and necessity of targeting BAs to enhance the survival of HCC patients.
Lü et al. (Wed,) studied this question.
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