Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
VIB-UGent Center for Inflammation Research, Ghent, Belgium.
Biochem Soc Trans. 2024 Apr 24;52(2):693-706. doi: 10.1042/BST20230550.
Pathological breakdown of membrane lipids through excessive lipid peroxidation (LPO) was first described in the mid-20th century and is now recognized as a form of regulated cell death, dubbed ferroptosis. Accumulating evidence unveils how metabolic regulation restrains peroxidation of phospholipids within cellular membranes, thereby impeding ferroptosis execution. Unleashing these metabolic breaks is currently therapeutically explored to sensitize cancers to ferroptosis inducing anti-cancer therapies. Reversely, these natural ferroptotic defense mechanisms can fail resulting in pathological conditions or diseases such as ischemia-reperfusion injury, multi-organ dysfunction, stroke, infarction, or neurodegenerative diseases. This minireview outlines current ferroptosis-inducing anti-cancer strategies and highlights the detection as well as the therapeutic targeting of ferroptosis in preclinical experimental settings. Herein, we also briefly summarize observations related to LPO, iron and redox deregulation in patients that might hint towards ferroptosis as a contributing factor.
细胞膜脂质通过过度脂质过氧化作用（LPO）的病理性破坏在 20 世纪中期首次被描述，现在被认为是一种受调控的细胞死亡形式，被称为铁死亡。越来越多的证据揭示了代谢调节如何抑制细胞膜内磷脂的过氧化作用，从而阻碍铁死亡的执行。目前正在探索释放这些代谢抑制来使癌症对诱导铁死亡的抗癌疗法敏感。相反，这些天然的铁死亡防御机制可能会失效，导致病理状况或疾病，如缺血再灌注损伤、多器官功能障碍、中风、梗塞或神经退行性疾病。本篇迷你综述概述了目前诱导铁死亡的抗癌策略，并强调了在临床前实验环境中对铁死亡的检测和治疗靶向。在此，我们还简要总结了与患者的 LPO、铁和氧化还原失调相关的观察结果，这些结果可能提示铁死亡是一个促成因素。
