27-Hydroxycholesterol in cancer development and drug resistance

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 con...

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Main Authors: Yaxin Hou, Zhiguang Fu, Chenhui Wang, Paulina Kucharzewska, Yuan Guo, Sihe Zhang
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Journal of Enzyme Inhibition and Medicinal Chemistry
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Online Access:https://www.tandfonline.com/doi/10.1080/14756366.2025.2507670
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author Yaxin Hou
Zhiguang Fu
Chenhui Wang
Paulina Kucharzewska
Yuan Guo
Sihe Zhang
author_facet Yaxin Hou
Zhiguang Fu
Chenhui Wang
Paulina Kucharzewska
Yuan Guo
Sihe Zhang
author_sort Yaxin Hou
collection DOAJ
description 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.
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publishDate 2025-12-01
publisher Taylor & Francis Group
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series Journal of Enzyme Inhibition and Medicinal Chemistry
spelling doaj-art-2c45cb397b734c25b8a24abd396cf3d32025-08-20T02:26:06ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742025-12-0140110.1080/14756366.2025.250767027-Hydroxycholesterol in cancer development and drug resistanceYaxin Hou0Zhiguang Fu1Chenhui Wang2Paulina Kucharzewska3Yuan Guo4Sihe Zhang5Department of Cell Biology, School of Medicine, Nankai University, Tianjin, ChinaDepartment of Tumor Radiotherapy, Air Force Medical Center, People’s Liberation Army of China (PLA), Beijing, ChinaDepartment of Cell Biology, School of Medicine, Nankai University, Tianjin, ChinaCenter of Cellular Immunotherapies, Warsaw University of Life Sciences, Warsaw, PolandDepartment of Cell Biology, School of Medicine, Nankai University, Tianjin, ChinaDepartment of Cell Biology, School of Medicine, Nankai University, Tianjin, China27-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.https://www.tandfonline.com/doi/10.1080/14756366.2025.250767027-Hydroxycholesterolenzymemetabolismcancer developmentdrug resistance
spellingShingle Yaxin Hou
Zhiguang Fu
Chenhui Wang
Paulina Kucharzewska
Yuan Guo
Sihe Zhang
27-Hydroxycholesterol in cancer development and drug resistance
Journal of Enzyme Inhibition and Medicinal Chemistry
27-Hydroxycholesterol
enzyme
metabolism
cancer development
drug resistance
title 27-Hydroxycholesterol in cancer development and drug resistance
title_full 27-Hydroxycholesterol in cancer development and drug resistance
title_fullStr 27-Hydroxycholesterol in cancer development and drug resistance
title_full_unstemmed 27-Hydroxycholesterol in cancer development and drug resistance
title_short 27-Hydroxycholesterol in cancer development and drug resistance
title_sort 27 hydroxycholesterol in cancer development and drug resistance
topic 27-Hydroxycholesterol
enzyme
metabolism
cancer development
drug resistance
url https://www.tandfonline.com/doi/10.1080/14756366.2025.2507670
work_keys_str_mv AT yaxinhou 27hydroxycholesterolincancerdevelopmentanddrugresistance
AT zhiguangfu 27hydroxycholesterolincancerdevelopmentanddrugresistance
AT chenhuiwang 27hydroxycholesterolincancerdevelopmentanddrugresistance
AT paulinakucharzewska 27hydroxycholesterolincancerdevelopmentanddrugresistance
AT yuanguo 27hydroxycholesterolincancerdevelopmentanddrugresistance
AT sihezhang 27hydroxycholesterolincancerdevelopmentanddrugresistance