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GRAPHICAL ABSTRACT
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PUBLIC SUMMARY
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Healthy cells use a precise multi-layered system to balance cholesterol production and clearance.
Cancer cells hijack cholesterol production, uptake, and storage to fuel tumor growth and spread.
Cholesterol imbalance in the tumor microenvironment (TME) rewires immune cells to suppress defenses.
Blocking cholesterol synthesis or restoring its balance boosts immune attack and drug sensitivity.
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ABSTRACT
Cholesterol constitutes an indispensable lipid metabolite for all eukaryotic cells and governs diverse core metabolic processes. Its homeostasis is precisely controlled by multilayered dynamic regulatory. Malignant cells subvert this homeostatic network to reprogram cholesterol synthesis, lipoprotein uptake and intracellular esterification, which collectively fuels tumorigenesis, metastasis and therapeutic resistance. Meanwhile, dysregulated cholesterol metabolism educates tumor microenvironment and induces immunosuppression especially by switching the polarization of tumor-associated macrophages. Therefore, targeting cholesterol metabolism has emerged as a highly promising anti-tumor strategy, in particular for the immunotherapy. This review focuses on the multi-layered regulatory mechanisms of cholesterol and its pathological roles in cancer, summarizes the latest advances in relevant targeted therapies, and elucidates the core value of cholesterol metabolism as a therapeutic vulnerability in cancer treatment.-
Keywords:
- Cholesterol metabolism /
- Tumorigenesis /
- Immunotherapy
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Lin L., Song P., Xie W., et al. (2026). Cholesterol metabolism implications for cancer and therapy. The Innovation Nutrition 1:100025. https://doi.org/10.59717/j.xinn-nutri.2026.100025
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Lin L., Song P., Xie W., et al. (2026). Cholesterol metabolism implications for cancer and therapy. The Innovation Nutrition 1:100025. https://doi.org/10.59717/j.xinn-nutri.2026.100025
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Figure 1.
Core cholesterol metabolic pathways in normal psychology
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Figure 2.
Cholesterol and its associated metabolites
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Figure 3.
Hierarchical dynamic regulatory network of cholesterol metabolism
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Figure 4.
Cholesterol metabolic reprogramming driving tumor progression and shaping the immunosuppressive TME
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Figure 5.
Roles of cholesterol and its associated metabolites in cell death
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Figure 6.
Pathological roles of dysregulated cholesterol metabolism in major diseases and crosstalk between metabolic disorders and cancer
