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The role of cholesterol metabolism in lung cancer
Weigang Xiu1, Xingyu Liu1,2, Kaixin Hu1,2
1Department of Thoracic Oncology and State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, China.
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. In this review, we summarized current research regarding the rule of cholesterol metabolism and therapeutic advances in lung cancer.
Insights
Altered cholesterol metabolism impacts lung cancer risk and progression. Targeting cholesterol pathways offers promising therapeutic strategies for lung cancer treatment.
Area of Science:
- Oncology
- Metabolic Research
- Biochemistry
Background:
- Elevated serum cholesterol metabolism correlates with reduced lung cancer risk.
- Disrupted cholesterol metabolism is observed in lung cancer patients and tumor cells.
- Cholesterol metabolism influences tumor cell growth, proliferation, and metastasis.
Purpose of the Study:
- To review the role of cholesterol metabolism in lung cancer.
- To summarize therapeutic advances targeting cholesterol metabolism in lung cancer.
Main Methods:
- Literature review of current research on cholesterol metabolism and lung cancer.
- Analysis of studies investigating therapeutic targets and drugs.
Main Results:
- Inhibiting cholesterol uptake or biosynthesis restrains lung tumor growth.
- Cholesterol metabolites (oxysterols, isoprenoids) regulate tumor cell metabolism.
- Cholesterol levels in the tumor microenvironment and cells impact cancer progression.
- Immune cell reprogramming is mediated by cholesterol metabolism effects.
Conclusions:
- Cholesterol metabolism is a critical factor in lung cancer development and progression.
- Targeting cholesterol metabolism, including statins and drugs affecting cholesterol transport, shows therapeutic promise for lung cancer.
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