Cuproptosis and prostate cancer: from molecular mechanisms and microenvironment remodeling to precision therapy.

Prostate cancer (PCa) is a leading malignancy, and progression to castration-resistant prostate cancer (CRPC) remains a central therapeutic challenge. Cuproptosis, a copper-dependent cell death mechanism first characterized in 2022, is triggered by copper binding to lipoylated tricarboxylic acid (TCA)-cycle proteins, inducing their aggregation, Fe-S cluster protein instability, and mitochondrial proteotoxic stress. This review critically evaluates the emerging but still heterogeneous evidence linking cuproptosis to PCa, explicitly distinguishing prostate cancer-specific data from pan-cancer,non-prostate, bioinformatic, and preclinical observations. We describe the core machinery, including ferredoxin 1 (FDX1), dihydrolipoamide acetyltransferase (DLAT), protein lipoylation enzymes, and copper transport/chaperone systems, while emphasizing differences from apoptosis and ferroptosis. In PCa, altered copper homeostasis and mitochondrial metabolic rewiring provide a biologically plausible vulnerability, but current evidence does not yet establish cuproptosis as a validated clinical driver or therapeutic target. We therefore summarize cuproptosis-related gene expression profiles and prognostic models as hypothesis-generating biomarkers, and provide a prostate cancer-specific evidence table that separates bioinformatic,