Open Access

REVIEW

The role of cholesterol metabolism in lung cancer

WEIGANG XIU^1,#, XINGYU LIU^1,2,#, KAIXIN HU^1,2, QIN ZHANG^3,*, HUASHAN SHI^4,*
1 Department of Thoracic Oncology and State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, China
2 West China School of Medicine, Sichuan University, Chengdu, 610041, China
3 Department of Postgraduate Students, West China School of Medicine, Chengdu, 610041, China
4 Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, China
* Corresponding Author: QIN ZHANG. Email: ; HUASHAN SHI. Email:
(This article belongs to the Special Issue: Metabolism of Cancer Cells and Immune Cells: A Balancing Action for Cancer Immunotherapy)

Oncology Research https://doi.org/10.32604/or.2024.047933

Received 22 November 2023; Accepted 04 March 2024; Published online 02 April 2024

Abstract

Elevated serum cholesterol metabolism is associated with a reduced risk of lung cancer. Disrupted cholesterol metabolism is evident in both lung cancer patients and tumor cells. Inhibiting tumor cell cholesterol uptake or biosynthesis pathways, through the modulation of receptors and enzymes such as liver X receptor and sterol-regulatory element binding protein 2, effectively restrains lung tumor growth. Similarly, promoting cholesterol excretion yields comparable effects. Cholesterol metabolites, including oxysterols and isoprenoids, play a crucial role in regulating cholesterol metabolism within tumor cells, consequently impacting cancer progression. In lung cancer patients, both the cholesterol levels in the tumor microenvironment and within tumor cells significantly influence cell growth, proliferation, and metastasis. The effects of cholesterol metabolism are further mediated by the reprogramming of immune cells such as T cells, B cells, macrophages, myeloid-derived suppressor cells, among others. Ongoing research is investigating drugs targeting cholesterol metabolism for clinical treatments. Statins, targeting the cholesterol biosynthesis pathway, are widely employed in lung cancer treatment, either as standalone agents or in combination with other drugs. Additionally, drugs focusing on cholesterol transportation have shown promise as effective therapies for lung cancer.

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Keywords

Cholesterol metabolism; Lung cancer; Immune cells; Targeted strategies

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