Regulation of m⁶A modification on ferroptosis and its potential significance in radiosensitization

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.