放疗常用于治疗各种类型的癌症，但放射抗性极大限制了其临床效率。最近的研究表明，放疗可以导致铁死亡（ferroptotic）癌细胞死亡。铁死亡是一种由过度脂质过氧化引起的新型程序性细胞死亡。诱导铁死亡为克服放射抗性提供了潜在的治疗策略。作为mRNA最常见的转录后修饰，m6A甲基化通过调节RNA功能广泛参与各种生理病理过程的调控。由m6A调控因子控制的动态m6A修饰还影响细胞对铁死亡的敏感性，从而决定肿瘤细胞对放疗的放射敏感性。在本综述中，我们总结了放疗诱导的铁死亡机制和意义，分析了m6A修饰对铁死亡的调控特点，并讨论了通过增强m6A介导的铁死亡来提高放射敏化的可能性。阐明m6A修饰对铁死亡的调控及其在肿瘤细胞对放疗反应中的意义，将有助于我们确定改善放疗效果和减轻或克服放射抗性的新靶点。 © 2023. 细胞死亡分化学会（ADMC）。

Radiotherapy is often used to treat various types of cancers, but radioresistance greatly limits the clinical efficiency. Recent studies have shown that radiotherapy can lead to ferroptotic cancer cell deaths. Ferroptosis is a new type of programmed cell death caused by excessive lipid peroxidation. The induction of ferroptosis provides a potential therapeutic strategy for radioresistance. As the most common post-transcriptional modification of mRNA, m6A methylation is widely involved in the regulation of various physiopathological processes by regulating RNA function. Dynamic m6A modification controlled by m6A regulatory factors also affects the susceptibility of cells to ferroptosis, thereby determining the radiosensitivity of tumor cells to radiotherapy. In this review, we summarize the mechanism and significance of radiotherapy induced ferroptosis, analyze the regulatory characteristics of m6A modification on ferroptosis, and discuss the possibility of radiosensitization by enhancing m6A-mediated ferroptosis. Clarifying the regulation of m6A modification on ferroptosis and its significance in the response of tumor cells to radiotherapy will help us identify novel targets to improve the efficacy of radiotherapy and reduce or overcome radioresistance.© 2023. Cell Death Differentiation Association (ADMC).