Radiotherapy plays a pivotal role in the treatment of malignant tumors. The emergence of radiation resistance in malignant tumors, contributing to tumor recurrence, progression, or distant metastasis, remains a significant treatment challenge. Exploring the mechanisms underlying radiation resistance and overcoming the radio-resistance of tumors have become urgent problems in oncological practice. Cuproptosis, a copper-dependent form of regulated cell death, is driven by the aggregation of lipoylated proteins and the reduction of Fe-S cluster proteins, etc. Copper and cuproptosis are not only intricately related to the incidence and development of tumors, but also participate in radiation resistance of tumor cells. Strategic interventions targeting copper and inducing cuproptosis will present promising avenues for overcoming radiation resistance and further improving the prognosis of tumor patients. This review comprehensively delineates established and potential mechanisms governing the intricate crosstalk between radiation resistance and cuproptosis, aiming to provide reference for overcoming radiation resistance in malignant tumor cells.

Radiotherapy plays a pivotal role in the treatment of malignant tumors. The emergence of radiation resistance in malignant tumors, contributing to tumor recurrence, progression, or distant metastasis, remains a significant treatment challenge. Exploring the mechanisms underlying radiation resistance and overcoming the radio-resistance of tumors have become urgent problems in oncological practice. Cuproptosis, a copper-dependent form of regulated cell death, is driven by the aggregation of lipoylated proteins and the reduction of Fe-S cluster proteins, etc. Copper and cuproptosis are not only intricately related to the incidence and development of tumors, but also participate in radiation resistance of tumor cells. Strategic interventions targeting copper and inducing cuproptosis will present promising avenues for overcoming radiation resistance and further improving the prognosis of tumor patients. This review comprehensively delineates established and potential mechanisms governing the intricate crosstalk between radiation resistance and cuproptosis, aiming to provide reference for overcoming radiation resistance in malignant tumor cells.