Liu Hu, Xue Hui, Guo Qian, Xue Xutong, Yang Lixue, Zhao Kaijun, Liu Yu'e
Department of Oncology Surgery, Shanghai Mengchao Hospital, Shanghai University, Shanghai, 202800, China.
Department of Rhinology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Cancer Lett. 2025 Jun 28;620:217696. doi: 10.1016/j.canlet.2025.217696. Epub 2025 Apr 4.
Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has emerged as a critical player in cancer pathogenesis. Concurrently, inflammation, a key biological response to tissue injury or infection, significantly influences cancer development and progression. The interplay between ferroptosis and inflammation represents a promising yet underexplored area of research. This review synthesizes recent advances in understanding the molecular mechanisms governing their interaction, emphasizing how ferroptosis triggers inflammatory responses and how inflammatory mediators, such as TNF-α, regulate ferroptosis through iron metabolism and lipid peroxidation pathways. Key molecular targets within the ferroptosis-inflammation axis, including GPX4, ACSL4, and the NF-κB signaling pathway, offer therapeutic potential for cancer treatment. By modulating these targets, it may be possible to enhance ferroptosis and fine-tune inflammatory responses, thereby improving therapeutic outcomes. Additionally, this review explores the broader implications of targeting the ferroptosis-inflammation interplay in disease treatment, highlighting opportunities for developing innovative strategies to combat cancer. By bridging the gap in current knowledge, this review provides a comprehensive resource for researchers and clinicians, offering insights into the therapeutic potential of this intricate biological relationship.
铁死亡是一种由脂质过氧化驱动的铁依赖性调节性细胞死亡形式，已成为癌症发病机制中的关键因素。同时，炎症作为对组织损伤或感染的关键生物学反应，显著影响癌症的发生和发展。铁死亡与炎症之间的相互作用是一个有前景但尚未充分探索的研究领域。本综述综合了在理解调控它们相互作用的分子机制方面的最新进展，强调了铁死亡如何引发炎症反应以及炎症介质（如肿瘤坏死因子-α）如何通过铁代谢和脂质过氧化途径调节铁死亡。铁死亡-炎症轴内的关键分子靶点，包括谷胱甘肽过氧化物酶4（GPX4）、长链脂酰辅酶A合成酶4（ACSL4）和核因子κB（NF-κB）信号通路，为癌症治疗提供了治疗潜力。通过调节这些靶点，有可能增强铁死亡并微调炎症反应，从而改善治疗效果。此外，本综述探讨了靶向铁死亡-炎症相互作用在疾病治疗中的更广泛意义，突出了开发对抗癌症创新策略的机会。通过弥合当前知识差距，本综述为研究人员和临床医生提供了全面的资源，深入了解这种复杂生物学关系的治疗潜力。
