Increasing evidence suggested that cholesterol is an important integrant of cell membranes, that plays a key role in tumor progression, immune dysregulation, and pathological changes in epigenetic mechanisms. Based on these theories, there is a growing interest on targeting cholesterol in the treatment of cancer. Here, we comprehensively reviewed the major function of cholesterol on oncogenicity, the therapeutic targets of cholesterol and its metabolites in cancer, and provide detailed insight into the essential roles of cholesterol in mediating immune and epigenetic mechanisms of the tumor microenvironment. It is also worth mentioning that the gut microbiome is an indispensable component of cancer mediation because of its role in cholesterol metabolism. Finally, we summarized recent studies on the potential targets of cholesterol and their metabolism, to provide more therapeutic interventions in oncology.

Mechanisms of cholesterol regulating tumorigenesis, which including (1). Cholesterol regulates oncogenic signaling in the membrane and cytoplasm. (2). The cholesterol metabolism pathway and its metabolites regulate cancer development. (3) The epigenetic and immune mechanisms of cholesterol regulation in cancer. (4). Gut microbes also have significant functions in cancer progressions.