Fig. 2

Role of ferroptosis in radiotherapy. Ionizing radiation can cause ferroptosis in several ways. DNA damage induced by ionizing radiation activates ATM and inhibits SLC7A11. DNA damage also activates the cGAS-STING signaling pathway and induces autophagy. Ionizing radiation induces ACSL4 expression and promotes the formation of lipid peroxidation substrates PUFA-PLs. Ionizing radiation causes ER stress, promotes p53 expression through PERK, and transcriptionally inhibits SLC7A11. Ionizing radiation also induces lipid peroxidation in adjacent cells through bystander effects by releasing RT-MPs and exosomes into the tumor microenvironment. ATM ataxia telangiectasia mutated protein, cGAS cyclic GMP–AMP synthase, STING stimulator of interferon genes protein, PERK PKR-like ER kinase, RT-MPs irradiated tumor cell-released microparticles