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Copper gluconate + disulfiram + temozolomide is an investigational small-molecule combination regimen being evaluated for the treatment of glioblastoma multiforme (GBM), including newly diagnosed and recurrent or temozolomide-resistant cases. The regimen combines the standard-of-care alkylating agent temozolomide with disulfiram (an FDA-approved alcohol-aversion drug) and copper gluconate (a dietary supplement). Mechanistically, the disulfiram-copper (DSF-Cu) complex acts as a potent inhibitor of the proteasome and O6-methylguanine-DNA methyltransferase (MGMT), a DNA repair enzyme that typically confers resistance to temozolomide. By inhibiting MGMT and downregulating DNA repair pathways, the combination aims to re-sensitize GBM cells to the DNA-damaging effects of temozolomide. Clinical development has reached Phase II, with studies conducted by institutions such as Wake Forest University and Cantex Pharmaceuticals.
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