Ediriweera Meran Keshawa
Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Colombo, Colombo 08, Sri Lanka.
Drug Discov Today. 2022 Nov;27(11):103347. doi: 10.1016/j.drudis.2022.103347. Epub 2022 Sep 7.
Irregularities in cholesterol metabolism occur in a range of human cancers. Cholesterol precursors and derivatives support tumorigenesis and weaken immune responses. Intriguing preclinical and clinical findings demonstrate that cholesterol biosynthesis inhibition achieved by targeting major events and metabolites in cholesterol metabolism is an ideal anti-tumor strategy. Investigations addressing the effects of β-hydroxy β-methylglutaryl-CoA (HMG-CoA) reductase (HMGCR), 2,3-oxidosqualene cyclase (OSC), squalene synthase (SQS), liver X receptors (LXR), and cholesterol trafficking and esterification inhibition on cancer progression have shown encouraging results. Notably, manipulation of cholesterol metabolism strengthens the function of immune cells in the tumor microenvironment (TME). In this review, I discuss the role of cholesterol metabolism in cancer progression and the latest research related to cholesterol metabolism-based anti-cancer therapies and intend to bring this stylish biochemistry topic to the Sri Lankan research landscape.
胆固醇代谢异常在一系列人类癌症中都会出现。胆固醇前体和衍生物会促进肿瘤发生并削弱免疫反应。有趣的临床前和临床研究结果表明,通过靶向胆固醇代谢中的主要事件和代谢产物来抑制胆固醇生物合成是一种理想的抗肿瘤策略。针对β-羟基-β-甲基戊二酰辅酶A(HMG-CoA)还原酶(HMGCR)、2,3-氧化角鲨烯环化酶(OSC)、鲨烯合酶(SQS)、肝脏X受体(LXR)以及胆固醇转运和酯化抑制对癌症进展的影响所进行的研究已取得了令人鼓舞的结果。值得注意的是,调控胆固醇代谢可增强肿瘤微环境(TME)中免疫细胞的功能。在这篇综述中,我将讨论胆固醇代谢在癌症进展中的作用以及与基于胆固醇代谢的抗癌疗法相关的最新研究,并打算将这个时髦的生物化学主题引入斯里兰卡的研究领域。