Cuproptosis in Triple-Negative Breast Cancer: Current Insights, Limitations and Copper-Related Therapeutic Perspectives

Cuproptosis, a recently identified form of copper-dependent regulated cell death, is closely associated with mitochondrial metabolism and copper homeostasis. Triple-negative breast cancer (TNBC) remains difficult to treat because of limited targeted therapeutic options and frequent therapeutic resistance. Emerging evidence suggests that cuproptosis-related pathways may influence TNBC progression, treatment response, and the tumor immune microenvironment. Preclinical studies further indicate that combining cuproptosis-targeting strategies with chemotherapy, targeted therapy, or immunotherapy may enhance anti-tumor efficacy. In this review, we summarize the molecular mechanisms of cuproptosis and its potential roles in TNBC progression, drug resistance, and immune regulation. We also discuss emerging therapeutic strategies targeting cuproptosis and their potential combination with existing treatments in TNBC. Finally, we highlight current challenges and future directions for the clinical translation of cuproptosis-based therapies in TNBC. Collectively, cuproptosis represents a promising but still evolving therapeutic vulnerability that requires further mechanistic and clinical validation.