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癌症中的铁死亡:机制、治疗策略及临床意义

Ferroptosis in cancer: Mechanisms, therapeutic strategies, and clinical implications.

作者信息

Pourhabib Mamaghani Mina, Mousavikia Seyedeh Nasibeh, Azimian Hosein

机构信息

Department of Medical Physics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Department of Medical Physics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Medical Physics Research Center, Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

Pathol Res Pract. 2025 May;269:155907. doi: 10.1016/j.prp.2025.155907. Epub 2025 Mar 12.

Abstract

The resistance of cancer cells to existing treatments has become a major challenge for researchers despite advancements in cancer treatment. Studies have shown that this resistance is due to cancer cells evading apoptosis. Moreover, the most common form of cell death induced by chemotherapy and radiotherapy is apoptosis. One of the most essential mechanisms cancer cells escape apoptosis is the excessive expression of tumors' apoptosis inhibitors. Therefore, finding a non-apoptotic pathway that bypasses apoptosis could be a hopeful strategy for cancer treatment. Ferroptosis has been identified as a non-apoptotic and regulated cell death process characterized by the accumulation of lipid peroxides and iron-dependent reactive oxygen species (ROS). Although studies have shown that ferroptosis plays a role in the development of many diseases, including cancer, it also has the potential to decrease resistance to current treatments, such as chemotherapy. Additionally, research has shown that ferroptosis successfully kills cancer cells, such as breast, stem, and lung cancer cells. Therefore, ferroptosis can be identified as a beneficial therapeutic mechanism for cancer treatment. Although ferroptosis has been introduced as an effective treatment path for cancer, its role, along with its therapeutic inducers, in increasing the therapeutic effect has not been investigated. In this review, we aim to introduce ferroptosis, compare it with other cell deaths known so far, and explain its role in cancer treatment. We believe that ferroptosis can be widely used to overcome cancer cells.

摘要

尽管癌症治疗取得了进展,但癌细胞对现有治疗方法的耐药性已成为研究人员面临的一项重大挑战。研究表明,这种耐药性是由于癌细胞逃避凋亡所致。此外,化疗和放疗诱导的最常见细胞死亡形式是凋亡。癌细胞逃避凋亡的最重要机制之一是肿瘤凋亡抑制剂的过度表达。因此,找到一条绕过凋亡的非凋亡途径可能是一种有希望的癌症治疗策略。铁死亡已被确定为一种非凋亡且受调控的细胞死亡过程,其特征是脂质过氧化物和铁依赖性活性氧(ROS)的积累。尽管研究表明铁死亡在包括癌症在内的许多疾病的发展中起作用,但它也有可能降低对当前治疗方法(如化疗)的耐药性。此外,研究表明铁死亡能成功杀死癌细胞,如乳腺癌、干细胞癌和肺癌细胞。因此,铁死亡可被视为一种有益的癌症治疗机制。尽管铁死亡已被引入作为一种有效的癌症治疗途径,但其作用以及其治疗诱导剂在提高治疗效果方面尚未得到研究。在这篇综述中,我们旨在介绍铁死亡,将其与目前已知的其他细胞死亡进行比较,并解释其在癌症治疗中的作用。我们相信铁死亡可广泛用于攻克癌细胞。

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