本综述旨在探讨富马酸水合酶（FH）相关肿瘤的铁死亡机制，以期为肿瘤的可能治疗提供依据。铁死亡是一种由细胞膜上的脂质过氧化引起的铁 (Fe) 依赖性调节细胞死亡形式。研究表明 FH 与肿瘤发生有关。由于 FH 基因突变会改变细胞代谢并增加肿瘤发生风险，特别是在肾脏中。由于大多数肿瘤细胞比正常细胞需要更多的亚铁离子 (Fe2+)，因此它们更容易出现铁死亡。最近的研究表明，铁死亡通过调节脂质和铁代谢、谷胱甘肽-谷胱甘肽过氧化物酶4（GSH-GPX4）、核因子-红细胞2相关因子2（NRF2）/血红素加氧酶来抑制FH缺陷型肿瘤的发病和进展。 -1 (HO-1) 途径。而FH缺陷的肿瘤细胞中Fe2+含量显着低于正常细胞。有望通过增加细胞内Fe2+浓度来促进铁死亡，从而达到治疗肿瘤的目的。本研究利用PubMed数据库检索铁死亡和FH缺陷型肿瘤的相关文章。FH是一种肿瘤抑制因子。多项基础研究表明，FH的缺失在遗传性平滑肌瘤和肾细胞癌、卵巢癌等肿瘤中起着重要作用。这类肿瘤细胞可以通过诱导铁死亡，抑制肿瘤细胞的增殖、迁移和侵袭，增加肿瘤细胞对化疗的敏感性，并通过多种分子机制逆转耐药性。目前，关于FH相关肿瘤铁死亡的研究还处于基础实验阶段。本文对FH和铁死亡的抗肿瘤作用及机制进行综述，以期进一步探讨铁死亡在FH相关肿瘤中的医学价值。 2024 年转化癌症研究。版权所有。

This review aims to investigate the ferroptosis mechanism of fumarate hydratase (FH)-related tumors for the purpose of possible treatment of tumors. Ferroptosis is an iron (Fe)-dependent form of regulated cell death caused by lipid peroxidation on the cell membrane. Studies have implicated FH in tumorigenesis. As mutations in the FH gene alter cellular metabolism and increase tumorigenesis risk, particularly in the kidneys. As most tumor cells require higher amounts of ferrous ions (Fe2+) than normal cells, they are more susceptible to ferroptosis. Recent studies have indicated that ferroptosis is inhibited the pathogenesis and progression of FH-deficient tumors by regulating lipid and iron metabolism, glutathione-glutathione peroxidase 4 (GSH-GPX4), nuclear factor-erythroid 2-related factor 2 (NRF2)/heme oxygenase-1 (HO-1) pathways. While the Fe2+ content is significantly lower in FH-deficient tumor cells, than that in normal cells. It is promising to promote ferroptosis by increasing the concentration of Fe2+ in cells to achieve the purpose of tumor treatment.In this study, we searched for relevant articles on ferroptosis and FH-deficient tumors using PubMed database.FH is a tumor suppressor. A number of basic studies have shown that the loss of FH plays an important role in hereditary leiomyomas and tumors such as renal cell carcinoma, ovarian cancer, and other tumors. This type of tumor cells can through induce ferroptosis, inhibit proliferation, migration and invasion of tumor cells, increase the sensitivity of tumor cells to chemotherapy, and reverse the drug resistance through various molecular mechanisms. At present, the research on ferroptosis in FH-related tumors is still in the basic experimental stage.This article reviews the anti-tumor effects and mechanisms of FH and ferroptosis, in order to further explore the medical value of ferroptosis in FH-related tumor therapy.2024 Translational Cancer Research. All rights reserved.