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| Cancer and cholesterol: friend or foe |
| Cancer Center, the First Hospital of Jilin University, Changchun 130021, Jilin, China |
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Abstract Cholesterol plays an important role in the body. The regulatory pathways mediated by LXR and SREBP2 can regulate intracellular cholesterol homeostasis by affecting cholesterol synthesis and metabolism. The tumor cells can enhance their ability of malignant proliferation, invasion, metastasis and adapt to the unfavorable living environment through metabolic reprogramming, in which the reprogramming of cholesterol metabolism plays a role, mainly manifested in the up-regulation of cholesterol synthesis in cancer cells and abnormal accumulation of their metabolites. Recent studies have shown that in the microenvironment of tumors, there is a reprogramming of cholesterol metabolism in the opposite trend of change, and its normal function is affected. Therapeutic strategies targeting cholesterol synthesis pathways also interfere with the normal metabolic homeostasis of immune cells. Therefore, looking for new antitumor drugs targeting different metabolic pathways is imminent. This review explores the roles and mechanisms of intracellular cholesterol homeostasis, cholesterol and its metabolites in the development of cancer, finding that modulators targeting cholesterol esters, 27-hydroxycholesterol, and Dendrogenin A may be potential targets of antitumor metabolic treatments. The cholesterol esterification inhibitor, Avasimibe has been shown to enhance immune system function and gets attention in antitumor metabolic therapy strategies. The proposed concept of anti-tumor metabolic therapy, which mainly regulates cholesterol metabolism of immune cells in the tumor microenvironment, delays cancer progression and metastasis, may bring new hope for the treatment of cancer patients.
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