Cuproptosis in gastric cancer: Mechanisms and therapeutic opportunities

Table 2 Evidence level and translational limitations

Strategy	Current evidence level	Main limitations
Copper ionophores	Gastric cancer-specific preclinical evidence; registered disulfiram/cisplatin gastric cancer trial is exploratory and has no posted results[61,85,86,90,97]	Narrow window, systemic toxicity, unclear patient selection, no mature gastric cancer efficacy data, and context-dependent mitochondrial metabolism[84-86]
Copper chelators	Mostly preclinical or early clinical evidence in non-GC malignancies; direct GC-specific clinical evidence remains limited[87,88]	Non-selective systemic copper depletion, potential neurological/hematological toxicity, and uncertain optimal combination schedules[87-89]
Copper-based or copper-modulating nanomedicine	Predominantly preclinical evidence in tumor models, with limited gastric cancer-specific validation[90-96]	Biodistribution, long-term safety, manufacturing reproducibility, and regulatory translation remain unresolved[89,91,93,95]
Combination therapy	Strong mechanistic rationale, but prospective biomarker-guided gastric cancer trials are still needed; clinical exploration remains limited[85,86,95]	Requires validated biomarkers, toxicity monitoring, dose optimization, and careful sequencing of treatment modalities[86,88,95]

Copper-modulating therapeutic strategies and translational challenges in gastric cancer. GC: Gastric cancer.