Department of Chemistry, The University of Chicago, Chicago, Illinois, 60637, United States.
Department of Radiation and Cellular Oncology and Ludwig Center for Metastasis Research, The University of Chicago, Chicago, Illinois, 60637, United States.
Angew Chem Int Ed Engl. 2024 Nov 11;63(46):e202412844. doi: 10.1002/anie.202412844. Epub 2024 Oct 4.
Cholesterol is an essential membrane component, and the metabolites from cholesterol play important biological functions to intricately support cancer progression and dampen immune responses. Preclinical and clinical studies have demonstrated the role of cholesterol metabolism regulation on inhibiting tumor growth, remodeling the immunosuppressive tumor microenvironment (TME), and enhancing anti-tumor immunity. In this minireview, we discuss complex cholesterol metabolism in tumors, its important role in cancer progression, and its influences on immune cells in the TME. We provide an overview of recent advances in cancer treatment through regulating cholesterol metabolism. We discuss the design of cholesterol-altering multifunctional nanomaterials to regulate oxidative stress, modulate immune checkpoints, manipulate mechanical stress responses, and alter cholesterol metabolic pathways. Additionally, we examine the interactions between cholesterol metabolism regulation and established cancer treatments with the aim of identifying efficient strategies to disrupt cholesterol metabolism and synergistic combination therapies for effective cancer treatment.
胆固醇是一种必需的膜成分，胆固醇的代谢产物发挥着重要的生物学功能，错综复杂地支持癌症的进展并抑制免疫反应。临床前和临床研究已经证明了调节胆固醇代谢在抑制肿瘤生长、重塑免疫抑制性肿瘤微环境（TME）和增强抗肿瘤免疫方面的作用。在这篇综述中，我们讨论了肿瘤中的复杂胆固醇代谢、其在癌症进展中的重要作用以及对 TME 中免疫细胞的影响。我们概述了通过调节胆固醇代谢治疗癌症的最新进展。我们讨论了设计改变胆固醇的多功能纳米材料来调节氧化应激、调节免疫检查点、操纵机械应激反应和改变胆固醇代谢途径的方法。此外，我们还研究了胆固醇代谢调节与现有癌症治疗方法之间的相互作用，旨在确定有效破坏胆固醇代谢的策略和协同联合治疗方法，以实现有效的癌症治疗。
