Defining the functions and translational potential of ferroptosis

我们发现，铁凋亡是一种新的受调控的非凋亡性细胞死亡形式， 已经确定了调节铁凋亡激活的主要机制， 它可以在致敏肿瘤中诱导。我们发现， 最终以脂质活性丧失后的过度脂质过氧化为特征 修复酶谷胱甘肽过氧化物酶4（Gpx4）。我们在此提出假设， 脂质过氧化作为一个信号，以检测缺乏营养所需的修复 氧化损伤，铁凋亡作为一种先天性肿瘤抑制 消除经历这种氧化应激的新生肿瘤的机制。我们进一步 建议阐明在特定癌症背景下驱动铁凋亡的机制， 是否可以制造精确的小分子铁凋亡激活剂， 消除对这种修复途径上瘾的肿瘤。

Ferroptosis in a new form of regulated, non-apoptotic cell death that we discovered; we have determined the major mechanisms regulating activation of ferroptosis and several contexts where it can be induced in sensitized tumors. We found that ferroptosis is ultimately characterized by excessive lipid peroxidation upon loss of activity of the lipid repair enzyme glutathione peroxidase 4 (Gpx4). We propose here the hypothesis that lipid peroxidation serves as a signal to detect a scarcity of nutrients needed tor repair of oxidative damage, and that ferroptosis serves as an innate tumor suppression mechanism to eliminate nascent tumors experiencing such oxidative stress. We further propose to elucidate mechanisms driving ferroptosis in specific cancer contexts, and whether it is feasible to create precision small molecule activators of ferroptosis that eliminate tumors that have become addicted to this repair pathway.