Figure 1.

Different forms of cancer cell death programs induced by RT. RT can directly damage the DNA through production and deposition of ionizing energy or indirectly via free radicals. The DNA strands can be damaged in single-strand and double-strand breaks. If these DNA lesions cannot be properly repaired, tumor cells will initiate different types of death programs, including mitotic catastrophe, apoptosis, and senescence. Ionizing radiation (IR) can induce not only the expression of ACSL4 but also the activation of p53, and hence, results in elevated ferroptosis. The ZBP1-RIPK3-MLKL necroptotic cascade induces accumulation of cytoplasmic mtDNA in irradiated tumor cells, and consequently, activates an anti-tumor immune response. Conversely, autophagy is more inclined to cause cancer cell survival following IR treatment. However, there is a need for further studies to determine whether RT can induce pyroptosis or cuproptosis. ACSL4—acyl-CoA synthetase long-chain family member 4; p53—tumor protein p53; ZBP1—Z-DNA-binding protein 1; RIPK3—receptor-interacting serine/threonine kinase 3; MLKL—mixed-lineage kinase domain-like pseudokinase; mtDNA—mitochondrial DNA.