Crosstalk between ferroptosis and cuproptosis: From mechanism to potential clinical application

Abstract

Ferroptosis and cuproptosis, regulated forms of cell death resulting from metal ion accumulation, are closely related in terms of occurrence, cell metabolism, signaling pathways, and drug resistance. Notably, it is now understood that these processes play crucial roles in regulating physiological and pathological processes, especially in tumor development. Consequently, ferroptosis and cuproptosis have gained increasing significance as potential targets for anti-cancer drug development. This article systematically outlines the molecular mechanisms and cross-talk components of both ferroptosis and cuproptosis, elucidating their impacts on cancer. Furthermore, it investigates the clinical perspective of targeted ferroptosis and cuproptosis in cancer chemotherapy, immunotherapy, and radiotherapy. Our discussion extends to a comparative analysis of nanoparticles developed based on the mechanisms of ferroptosis and cuproptosis in cancer, contrasting them with current conventional therapies. Opportunities and challenges in cancer treatment are explored, emphasizing the potential therapeutic direction of co-targeting ferroptosis and cuproptosis. The article also attempts to analyze the clinical applications of this co-targeting approach for cancer treatment while summarizing the existing barriers that require overcoming.