铁死亡调控机理及其在肿瘤治疗中的应用

 铁死亡（ferroptosis）为最近鉴定出的一种新的细胞程序性死亡模式，越来越多证据表明铁死亡在肿瘤的发生发展中扮演了重要角色。综述了近年来铁死亡的调控机制研究进展，包括经典和非经典的铁死亡诱导过程、活性氧自由基（reactive oxygen species，ROS）及非编码RNA在铁死亡调控中的作用。论述了铁死亡与肿瘤的关系，包括肿瘤抑制因子、缺氧诱导因子、NRF2和细胞间质化状态参与铁死亡敏感性的调控，以及利用铁死亡来靶向治疗肿瘤，介绍了研发出的4类铁死亡诱导剂：I、II、III和IV型。总结了可能的肿瘤细胞抵抗铁死亡的机制，为靶向这一新的细胞死亡模式提供分子依据，从而提高肿瘤治疗效果。

The mechanism of ferroptosis and its application to cancer therapy

Ferroptosis has been recently identified as the necrotic cell death marked by oxidative modification that is irondependent, and morphologically, biochemically and genetically different from other established cell deaths. More and more evidences demonstrate that ferroptosis plays an important role in cancer progression. This review summarizes recent advances in the study of the regulatory mechanisms in ferroptosis, mainly divided into classical and non-classical ferroptosis-inducing processes, and the function of ROS and non-coding RNAs in the regulation of ferroptosis. The relationship between ferroptosis and tumors is highlighted, including the involvement of tumor suppressors, hypoxia-inducible factors, NRF2 and cell epithelialmesenchymal transformation status in regulation of ferroptosis sensitivity, use of ferroptosis to target tumors, and development of four classes of ferroptosis inducers: types I, II, III and IV. Finally, the mechanisms are summarized by which ferroptosis can be possibly regulated in cancer cells, and how to conquer the ferroptosis resistance is also prospected to eventually promote ferroptosis as a new promising way to kill therapy-resistant cancers.