Shayanmanesh Maryam, Ahmadi Seyed Esmaeil, Amini Ali
Department of Hematology and Blood Banking, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran.
Department of Endocrinology, Diabetology, and Clinical Nutrition, University Hospital Zurich (USZ) and University of Zurich (UZH), Zurich, Switzerland.
J Cell Mol Med. 2025 Sep;29(17):e70790. doi: 10.1111/jcmm.70790.
Haematological malignancies encompass a wide spectrum of blood cell disorders with diverse prognoses. Despite recent advances in therapy, many of these disorders remain incurable or exhibit relapse and drug resistance. Ferroptosis, an iron-dependent form of cell death caused by lipid peroxidation, holds promise as a strategy to overcome the resistance seen with conventional therapies. This review aims to succinctly outline current research concerning the regulatory function of ferroptosis-related genes (FRGs) and various types of non-coding RNAs (ncRNAs), as well as various types of ferroptosis inducers (FINs), encompassing small molecule compounds, natural derivatives, synthetic agents and nanoparticles. The exploration delves into the mechanisms by which FINs operate, including inhibiting the system Xc, deactivating the enzyme glutathione peroxidase 4 (GPX4), disrupting glutathione (GSH) production and interfering with iron or lipid metabolism. The investigation emphasises the functioning of these agents and the underlying molecular processes driving the initiation of ferroptosis. A comprehensive assessment reveals the potential utility of FINs as innovative treatments for haematological neoplasms, offering insights into a novel therapeutic approach.
血液系统恶性肿瘤包括多种预后各异的血细胞疾病。尽管近期治疗取得了进展,但许多此类疾病仍无法治愈,或会出现复发及耐药情况。铁死亡是一种由脂质过氧化引起的铁依赖性细胞死亡形式,有望成为克服传统疗法耐药性的一种策略。本综述旨在简要概述当前关于铁死亡相关基因(FRGs)和各类非编码RNA(ncRNAs)的调控功能,以及各类铁死亡诱导剂(FINs)的研究,包括小分子化合物、天然衍生物、合成剂和纳米颗粒。该探索深入研究了FINs发挥作用的机制,包括抑制胱氨酸/谷氨酸反向转运体系统(system Xc)、使谷胱甘肽过氧化物酶4(GPX4)失活、破坏谷胱甘肽(GSH)生成以及干扰铁或脂质代谢。研究强调了这些药剂的作用以及驱动铁死亡起始的潜在分子过程。全面评估揭示了FINs作为血液系统肿瘤创新治疗方法的潜在效用,为一种新型治疗方法提供了见解。