27-Hydroxycholesterol in cancer development and drug resistance

作者：Yaxin Hou, Zhiguang Fu, Chenhui Wang, Paulina Kucharzewska, Yuan Guo, Sihe Zhang · 发表于：Journal of Enzyme Inhibition and Medicinal Chemistry · 年份：2025 · DOI：10.1080/14756366.2025.2507670 · 被引用次数：5 · 研究领域：Cancer, Lipids, and Metabolism、Cholesterol and Lipid Metabolism、Estrogen and related hormone effects

27-Hydroxycholesterol (27HC), a cholesterol metabolite, functions both as a selective oestrogen receptor (ER) modulator and a ligand for liver X receptors (LXRs). The discovery of 27HC involvement in carcinogenesis has unveiled new research avenues, yet its precise role remains controversial and context-dependent. In this review, we provide an overview of the biosynthesis and metabolism of 27HC and explore its cancer-associated signalling, with a particular focus on ER- and LXR-mediated pathways. Given the tissue-specific dual role of 27HC, we discuss its differential impact across various cancer types. Furthermore, we sort out 27HC-contributed drug resistance mechanisms from the perspectives of drug efflux, cellular proliferation, apoptosis, epithelial-mesenchymal transition (EMT), antioxidant defence, epigenetic modification, and metabolic reprogramming. Finally, we highlight the chemical inhibitors to mitigate 27HC-driven cancer progression and drug resistance. This review offers an updated role of 27HC in cancer biology, setting the stage for future research and the development of targeted therapeutics.