Ferroptosis and Cuproptosis in the Pathogenesis of Breast Cancer: Molecular Mechanisms, Crosstalk, and Therapeutic Perspectives

The essay reviews current understanding of the role of metal-dependent forms of regulated cell death – ferroptosis and cuproptosis – in the pathogenesis of breast cancer and their therapeutic potential. The aim of the work was to analyze the molecular mechanisms of both processes, identify common regulatory nodes, and assess the prospects for their joint targeting to overcome chemoresistance. Methodologically, the work is based on a critical review of peer-reviewed scientific sources devoted to ferroptosis, cuproptosis, and their cross-talk in the context of oncology. It has been shown that ferroptosis, iron-dependent lipid peroxidation, and cuproptosis, copper-dependent proteotoxic death, have common regulatory nodes, in particular, glutathione metabolism, mitochondrial respiration, and the p53 signaling pathway. It has been established that induction of both processes allows overcoming resistance to cisplatin, doxorubicin, and taxanes, especially in aggressive subtypes such as triple-negative breast cancer. Current therapeutic strategies are reviewed, including the use of nanocarriers for targeted delivery of ferroptosis and cuproptosis inducers, as well as the results of clinical trials of disulfiram, elesclomol, and copper chelators. At the same time, limitations of clinical translation are emphasized: the lack of validated biomarkers, the risk of systemic toxicity, and tumor heterogeneity. It is concluded that co-targeting ferroptosis and cuproptosis is a promising strategy, but its widespread clinical application requires further prospective studies, biomarker identification, and development of targeted nanosystems.