Cuproptosis in gastric cancer: Mechanisms and therapeutic opportunities

Table 1 Representative agents/platforms and proposed mechanisms

Strategy	Representative agents/platforms and evidence	Proposed mechanism
Copper ionophores	Elesclomol; disulfiram/copper (DSF/Cu); cisplatin plus disulfiram for advanced gastric cancer (NCT05667415; not yet recruiting; no results posted)[83-86]	Increase intracellular copper, promote mitochondrial stress, induce cuproptosis-related or ROS-dependent cytotoxicity, and enhance chemotherapy response[31,61,83,84,86]
Copper chelators	Tetrathiomolybdate, D-penicillamine, triethylenetetramine/tetraethylenepentamine[87-89]	Reduce copper bioavailability, inhibit copper-driven angiogenesis, and may modulate immune checkpoint signaling and tumor vascularization[16,87-89]
Copper-based or copper-modulating nanomedicine	CuO nanoparticles, elesclomol-loaded copper oxide nanoplatforms, CuMoO4-based systems, mitochondria-targeted copper-depleting nanoparticles[90-96]	Improve tumor-targeted copper delivery or depletion, induce mitochondrial stress/cuproptosis, and enable combination with photothermal therapy, chemotherapy, or immunotherapy[90-96]
Combination therapy	Copper modulation plus chemotherapy, immune checkpoint blockade, targeted therapy, or photothermal therapy[17,88,90,94,95]	May overcome drug resistance, reshape the tumor microenvironment, and convert immunologically cold tumors into more responsive phenotypes[17,88,90,93,95]

Copper-modulating therapeutic strategies and translational challenges in gastric cancer. ROS: Reactive oxygen species.