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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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/14756366.2025.2507670 |
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| _version_ | 1850151957152399360 |
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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. |
| format | Article |
| id | doaj-art-2c45cb397b734c25b8a24abd396cf3d3 |
| institution | OA Journals |
| issn | 1475-6366 1475-6374 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| 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 |
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