Role of Cholesterol Metabolism in the Anticancer Pharmacology of Selective Estrogen Receptor Modulators

Selective estrogen receptor modulators (SERMs) are a class of compounds that bind to estrogen receptors (ERs) and possess estrogen agonist or antagonist actions in different tissues. As such, they are widely used drugs. For instance, tamoxifen, the most prescribed SERM, is used to treat ERα-positive breast cancer. Aside from their therapeutic targets, SERMs have the capacity to broadly affect cellular cholesterol metabolism and handling, mainly through ER-independent mechanisms. Cholesterol metabolism reprogramming is crucial to meet the needs of cancer cells, and different key processes involved in cholesterol homeostasis have been associated with cancer progression. Therefore, the effects of SERMs on cholesterol homeostasis may be relevant to carcinogenesis, either by contributing to the anticancer efficacy of these compounds or, conversely, by promoting resistance to treatment. Understanding these aspects of SERMs actions could help to design more efficacious therapies. Herein we review the effects of SERMs on cellular cholesterol metabolism and handling and discuss their potential in anticancer pharmacology.