Department of Thoracic Oncology and State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, China.
West China School of Medicine, Sichuan University, Chengdu, 610041, China.
Oncol Res. 2024 Sep 18;32(10):1613-1621. doi: 10.32604/or.2024.047933. eCollection 2024.
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.
血清胆固醇代谢升高与肺癌风险降低有关。胆固醇代谢紊乱在肺癌患者和肿瘤细胞中都很明显。通过调节受体和酶，如肝 X 受体和固醇调节元件结合蛋白 2，抑制肿瘤细胞胆固醇摄取或生物合成途径，可有效抑制肺肿瘤生长。同样，促进胆固醇排泄也会产生类似的效果。胆固醇代谢物，包括氧化固醇和异戊二烯，在调节肿瘤细胞内胆固醇代谢中发挥着关键作用，从而影响癌症的进展。在肺癌患者中，肿瘤微环境和肿瘤细胞内的胆固醇水平都显著影响细胞生长、增殖和转移。胆固醇代谢的作用还通过 T 细胞、B 细胞、巨噬细胞、髓样来源的抑制细胞等免疫细胞的重编程来介导。目前正在研究针对胆固醇代谢的药物用于临床治疗。他汀类药物，靶向胆固醇生物合成途径，广泛用于肺癌的治疗，无论是作为单一药物还是与其他药物联合使用。此外，专注于胆固醇运输的药物作为有效的肺癌治疗方法也显示出了希望。在这篇综述中，我们总结了胆固醇代谢的规律和肺癌治疗的最新进展。
