Provoking cancer cell cuproptosis breaks radiotherapy resistance

Radiation induces multiple forms of cell death that critically govern therapeutic efficacy and antitumor immunity. Although apoptosis is the primary cell death pathway mediated by radiation, it paradoxically promotes immune evasion and radioresistance. This underscores the need to identify dominant cell death pathways underlying radioresistance to address clinical radiotherapy bottlenecks. In the current issue of Cancer Cell, Lei et al. demonstrate that radiation-induced ​​cuproptosis​​ is a mechanism to overcome radioresistance. Here, we focus on the emerging cross-talk between radiotherapy and cuproptosis evasion, discuss immunomodulatory death pathway networks in radiotherapy, and also emphasize that future studies should elucidate the role of cuproptosis in orchestrating radiotherapy-induced immune responses.