Researchers have found that a repurposed drug combination of disulfiram and copper may help overcome chemotherapy resistance in pancreatic cancer, one of the most lethal cancer types.
The study focuses on pancreatic ductal adenocarcinoma, where resistance to the chemotherapy drug 5-fluorouracil (5-FU) often limits the effectiveness of standard treatment regimens like FOLFIRINOX. Scientists discovered that disulfiram, an FDA-approved drug originally used to treat alcohol dependence, becomes highly toxic to cancer cells when paired with copper.
The combination worked against both standard and 5-FU–resistant pancreatic cancer cells by disrupting key survival pathways. It weakened the cancer cells’ antioxidant defenses, altered stress-related signaling networks, and triggered programmed cell death. In resistant tumors, the treatment also reduced harmful oxidative stress and activated cell-destruction pathways.
In mouse models, treatment with disulfiram and copper dramatically reduced tumor growth compared to untreated animals, with tumor sizes shrinking to a fraction of those in control groups.
Researchers noted that further studies are needed before human trials, particularly to improve drug delivery and ensure safety, as current models do not fully replicate the human tumor environment.