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.

选择性雌激素受体调节剂 (SERM) 是一类与雌激素受体 (ER) 结合并在不同组织中具有雌激素激动或拮抗作用的化合物。因此，它们是广泛使用的药物。例如，他莫昔芬是处方最多的 SERM，用于治疗 ERα 阳性乳腺癌。除了它们的治疗靶点之外，SERM 还具有广泛影响细胞胆固醇代谢和处理的能力，主要是通过 ER 非依赖性机制。胆固醇代谢重编程对于满足癌细胞的需求至关重要，而胆固醇稳态中涉及的不同关键过程与癌症进展有关。因此，SERMs 对胆固醇稳态的影响可能与致癌作用有关，要么通过促进这些化合物的抗癌功效，要么相反，通过促进对治疗的抵抗力。了解 SERM 作用的这些方面有助于设计更有效的疗法。在这里，我们回顾了 SERM 对细胞胆固醇代谢和处理的影响，并讨论了它们在抗癌药理学中的潜力。