Gao Weijuan, Tan Jiani, Yu Chengtao
The First Clinical School of Nanjing University of Chinese Medicine, Nanjing, China.
Front Oncol. 2025 Aug 22;15:1650219. doi: 10.3389/fonc.2025.1650219. eCollection 2025.
Ferroptosis is a regulated, non-apoptotic form of cell death marked by the accumulation of iron-dependent lipid peroxides. This process causes rapid rupture of the plasma membrane and the release of intracellular contents. Ferroptosis acts as an intrinsic tumor-suppressive mechanism. It plays a crucial role in tumor progression, metastasis, and resistance to standard therapies, including chemotherapy and radiotherapy. Its unique molecular mechanisms confer significant therapeutic potential. In recent years, multiple experimental therapies aiming to induce ferroptosis have been developed for cancer treatment. Although these therapies show promise in controlling tumor growth, their effects on the tumor microenvironment (TME) require further investigation. Recent studies indicate that distinct cell populations within the TME have different sensitivities to ferroptosis. This variability may lead to unintended effects, such as damage to normal cells or increased inflammation, resulting in toxicity. Cells in the TME can either undergo ferroptosis or modulate its regulation through intercellular signaling and interactions. Notably, ferroptosis-related interactions between tumor cells and other components of the TME, such as immune cells, stromal cells, and endothelial cells, are central to TME remodeling. This mini-review summarizes recent advances in ferroptosis mechanisms and highlights the dynamic interplay between ferroptosis and the TME. It also discusses the prospects and challenges of ferroptosis-based cancer therapies.
铁死亡是一种受调控的非凋亡性细胞死亡形式，其特征是铁依赖性脂质过氧化物的积累。这个过程会导致质膜迅速破裂并释放细胞内物质。铁死亡作为一种内在的肿瘤抑制机制，在肿瘤进展、转移以及对包括化疗和放疗在内的标准疗法的抗性中发挥着关键作用。其独特的分子机制具有显著的治疗潜力。近年来，已开发出多种旨在诱导铁死亡的实验性疗法用于癌症治疗。尽管这些疗法在控制肿瘤生长方面显示出前景，但它们对肿瘤微环境（TME）的影响仍需进一步研究。最近的研究表明，TME内不同的细胞群体对铁死亡具有不同的敏感性。这种变异性可能会导致意外的影响，如对正常细胞的损伤或炎症增加，从而产生产生毒性。TME中的细胞可以经历铁死亡，也可以通过细胞间信号传导和相互作用来调节其调控。值得注意的是，肿瘤细胞与TME的其他成分（如免疫细胞、基质细胞和内皮细胞）之间与铁死亡相关的相互作用是TME重塑的核心。本综述总结了铁死亡机制的最新进展，强调了铁死亡与TME之间的动态相互作用。它还讨论了基于铁死亡的癌症疗法的前景和挑战。
