Hou Kai, Liu Lin, Fang Zhi-Hui, Zong Wei-Xing, Sun Daqiang, Guo Zhigang, Cao Lu
Tianjin Medical University, Tianjin, 300070, China.
Tianjin Chest Hospital, Tianjin, 300222, China.
Arch Toxicol. 2024 Mar;98(3):709-734. doi: 10.1007/s00204-023-03665-3. Epub 2024 Jan 5.
With the rapid development of new generations of antitumor therapies, the average survival time of cancer patients is expected to be continuously prolonged. However, these therapies often lead to cardiotoxicity, resulting in a growing number of tumor survivors with cardiovascular disease. Therefore, a new interdisciplinary subspecialty called "cardio-oncology" has emerged, aiming to detect and treat cardiovascular diseases associated with tumors and antitumor therapies. Recent studies have highlighted the role of ferroptosis in both cardiovascular and neoplastic diseases. The balance between intracellular oxidative stress and antioxidant defense is crucial in regulating ferroptosis. Tumor cells can evade ferroptosis by upregulating multiple antioxidant defense pathways, while many antitumor therapies rely on downregulating antioxidant defense and promoting ferroptosis in cancer cells. Unfortunately, these ferroptosis-inducing antitumor therapies often lack tissue specificity and can also cause injury to the heart, resulting in ferroptosis-induced cardiotoxicity. A range of cardioprotective agents exert cardioprotective effects by inhibiting ferroptosis. However, these cardioprotective agents might diminish the efficacy of antitumor treatment due to their antiferroptotic effects. Most current research on ferroptosis only focuses on either tumor treatment or heart protection but rarely considers both in concert. Therefore, further research is needed to study how to protect the heart during antitumor therapies by regulating ferroptosis. In this review, we summarized the role of ferroptosis in the treatment of neoplastic diseases and cardiovascular diseases and also attempted to propose further research directions for ferroptosis in the field of cardio-oncology.
随着新一代抗肿瘤疗法的迅速发展，癌症患者的平均生存时间有望持续延长。然而，这些疗法常常导致心脏毒性，致使患心血管疾病的肿瘤幸存者数量不断增加。因此，一个名为“心脏肿瘤学”的新兴跨学科亚专业应运而生，旨在检测和治疗与肿瘤及抗肿瘤疗法相关的心血管疾病。最近的研究突出了铁死亡在心血管疾病和肿瘤性疾病中的作用。细胞内氧化应激与抗氧化防御之间的平衡对于调节铁死亡至关重要。肿瘤细胞可通过上调多种抗氧化防御途径来逃避铁死亡，而许多抗肿瘤疗法则依赖于下调抗氧化防御并促进癌细胞的铁死亡。不幸的是，这些诱导铁死亡的抗肿瘤疗法往往缺乏组织特异性，还会对心脏造成损伤，导致铁死亡诱导的心脏毒性。一系列心脏保护剂通过抑制铁死亡发挥心脏保护作用。然而，这些心脏保护剂可能因其抗铁死亡作用而降低抗肿瘤治疗的疗效。目前大多数关于铁死亡的研究仅专注于肿瘤治疗或心脏保护，很少同时兼顾两者。因此，需要进一步研究如何通过调节铁死亡在抗肿瘤治疗期间保护心脏。在这篇综述中，我们总结了铁死亡在肿瘤性疾病和心血管疾病治疗中的作用，并试图为心脏肿瘤学领域中铁死亡的进一步研究方向提出建议。
