Targeting lipid metabolism for ferroptotic cancer therapy
Targeting lipid metabolism for ferroptotic cancer therapy
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DOI：
10.1007/s10495-022-01795-0
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发表时间：
2022-11
期刊：
影响因子：
7.2
通讯作者：
Minhua Luo;Jia-Qi Yan;Xinyu Hu;Haolong Li;Hongsheng Li;Quentin Liu;Yibing Chen;Zhengzhi Zou
中科院分区：
文献类型：
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作者：
Minhua Luo;Jia-Qi Yan;Xinyu Hu;Haolong Li;Hongsheng Li;Quentin Liu;Yibing Chen;Zhengzhi Zou
铁凋亡的概念提出至今已有10年的时间，对铁凋亡的研究也在不断增加。铁凋亡是由铁依赖性脂质过氧化作用驱动的，其可被谷胱甘肽过氧化物酶4（GPX4）、铁凋亡抑制蛋白1（FSP1）、二氢乳清酸脱氢酶（DHODH）和Fas相关因子1（FAF1）拮抗。各种细胞代谢事件，包括脂质代谢，可以调节铁凋亡敏感性。值得注意的是，癌细胞脂质代谢的重编程可以促进肿瘤的发生和发展。癌细胞的代谢灵活性为协调靶向多种脂质代谢途径以触发癌细胞铁凋亡提供了可能性。此外，癌细胞必须获得永生，逃避包括铁凋亡在内的程序性细胞死亡，以促进癌症进展，这为改善癌症治疗提供了新的视角。靶向铁凋亡的脆弱性已经受到关注，作为治疗癌症的重要可能策略之一，因为其在调节肿瘤细胞存活中的作用。本文综述了铁和脂质代谢对铁凋亡的影响，以及脂质代谢重编程和铁凋亡的相互作用在抗肿瘤免疫中的潜在作用，并总结了针对脂质代谢和铁凋亡的药物在肿瘤治疗中的应用。
It has been 10 years since the concept of ferroptosis was put forward and research focusing on ferroptosis has been increasing continuously. Ferroptosis is driven by iron-dependent lipid peroxidation, which can be antagonized by glutathione peroxidase 4 (GPX4), ferroptosis inhibitory protein 1 (FSP1), dihydroorotate dehydrogenase (DHODH) and Fas-associated factor 1 (FAF1). Various cellular metabolic events, including lipid metabolism, can modulate ferroptosis sensitivity. It is worth noting that the reprogramming of lipid metabolism in cancer cells can promote the occurrence and development of tumors. The metabolic flexibility of cancer cells opens the possibility for the coordinated targeting of multiple lipid metabolic pathways to trigger cancer cells ferroptosis. In addition, cancer cells must obtain immortality, escape from programmed cell death including ferroptosis, to promote cancer progression, which provides new perspectives for improving cancer therapy. Targeting the vulnerability of ferroptosis has received attention as one of the significant possible strategies to treat cancer given its role in regulating tumor cell survival. We review the impact of iron and lipid metabolism on ferroptosis and the potential role of the crosstalk of lipid metabolism reprogramming and ferroptosis in antitumor immunity and sum up agents targeting lipid metabolism and ferroptosis for cancer therapy.