Zhao Jingyu, Wang Yaqi, Tao Lei, Chen Ligong
School of Pharmaceutical Sciences, Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Tsinghua University, Beijing, China.
Collaborative Innovation Center for Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
Front Oncol. 2022 Apr 21;12:861834. doi: 10.3389/fonc.2022.861834. eCollection 2022.
Malignant brain tumors represent approximately 1.5% of all malignant tumors. The survival rate among patients is relatively low and the mortality rate of pediatric brain tumors ranks first among all childhood malignant tumors. At present malignant brain tumors remain incurable. Although some tumors can be treated with surgery and chemotherapy, new treatment strategies are urgent owing to the poor clinical prognosis. Iron is an essential trace element in many biological processes of the human body. Iron transporters play a crucial role in iron absorption and transport. Ferroptosis, an iron-dependent form of nonapoptotic cell death, is characterized by the accumulation of lipid peroxidation products and lethal reactive oxygen species (ROS) derived from iron metabolism. Recently, compelling evidence has shown that inducing ferroptosis of tumor cells is a potential therapeutic strategy. In this review, we will briefly describe the significant regulatory factors of ferroptosis, iron, its absorption and transport under physiological conditions, especially the function of iron transporters. Then we will summarize the relevant mechanisms of ferroptosis and its role in malignant brain tumors, wherein the role of transporters is not to be ignored. Finally, we will introduce the current research progress in the treatment of malignant brain tumors by inducing ferroptosis in order to explain the current biological principles of potential treatment targets and treatment strategies for malignant brain tumors.
恶性脑肿瘤约占所有恶性肿瘤的1.5%。患者的生存率相对较低,儿童脑肿瘤的死亡率在所有儿童恶性肿瘤中位居首位。目前,恶性脑肿瘤仍然无法治愈。尽管一些肿瘤可以通过手术和化疗进行治疗,但由于临床预后较差,新的治疗策略迫在眉睫。铁是人体许多生物过程中必需的微量元素。铁转运蛋白在铁的吸收和运输中起着关键作用。铁死亡是一种铁依赖性的非凋亡性细胞死亡形式,其特征是脂质过氧化产物和源自铁代谢的致命活性氧(ROS)的积累。最近,有力的证据表明,诱导肿瘤细胞铁死亡是一种潜在的治疗策略。在这篇综述中,我们将简要描述铁死亡的重要调节因子、铁及其在生理条件下的吸收和运输,特别是铁转运蛋白的功能。然后,我们将总结铁死亡的相关机制及其在恶性脑肿瘤中的作用,其中转运蛋白的作用不容忽视。最后,我们将介绍通过诱导铁死亡治疗恶性脑肿瘤的当前研究进展,以解释恶性脑肿瘤潜在治疗靶点和治疗策略的当前生物学原理。
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