Copper homeostasis imbalance and cuproptosis: Emerging targets and strategies for gastrointestinal tumor therapy

Figure 6 Clinical translation roadmap for precision cuproptosis-targeted therapy. Precision cuproptosis therapy requires patient stratification according to ferredoxin 1 expression, protein lipoylation status, and metabolic phenotype. Tumors with high ferredoxin 1/Lipoylation and oxidative phosphorylation dependence may respond to copper ionophore-based therapy, whereas glycolytic or stromal-rich resistant tumors may require metabolic rewiring, stroma remodeling, or nanodelivery strategies. Protective agents such as selenium may further improve the therapeutic window by reducing off-target hepato-renal toxicity. FDX1: Ferredoxin 1; DLAT: Dihydrolipoamide S-acetyltransferase; LIAS: Lipoic acid synthase; TCA: Tricarboxylic acid cycle; OXPHOS: Oxidative phosphorylation; PDK: Pyruvate dehydrogenase kinase; ECM: Extracellular matrix.