Copper Metabolism and Cuproptosis in Ovarian Cancer

Objectives: This review provides a comprehensive analysis of copper metabolism and cuproptosis in ovarian cancer (OC), evaluating therapeutic strategies targeting copper to improve clinical outcomes. Mechanism: OC exhibits the highest mortality rate among gynecological malignancies, characterized by its insidious onset and poor prognosis, underscoring the urgent need for novel treatment strategies. Copper metabolism and cuproptosis hold promising potential in regulating tumor progression and overcoming drug resistance, thereby opening new avenues for OC treatment. This article aims to elucidate the biological basis and potential therapeutic applications of copper metabolism and cuproptosis in treating OC. Findings in Brief: Cuproptosis, a copper-dependent mechanism of cell death mechanism, disrupts mitochondrial function by inducing the aggregation of lipoylated proteins and the loss of iron-sulfur (Fe-S) clusters. Copper metabolism imbalance promotes OC progression by modulating cancer cell function, contributing to chemotherapy resistance, and influencing responses to anti-angiogenesis, and immunotherapy. Copper ionophores, chelators, copper-based nanoparticles (NPs), and certain natural molecules represent potential therapeutic strategies for the treatment of OC. Conclusions: Targeting copper metabolism and cuproptosis offers innovative therapeutic strategies for OC, particularly in cases of treatment resistance. However, clinical validation of long-term safety, optimal dosing, and biomarker-guided therapies remains critical. Future research should prioritize translational studies to bridge mechanistic insights with patient-centered applications.