Disulfiram and the challenges of modern medicine – new directions and possibilities

Disulfiram, originally developed for the treatment of alcohol dependence, has recently gained attention for its potential applications in oncology and infectious diseases. In breast and pancreatic cancers, disulfiram forms copper complexes that inhibit tumor growth, induce oxidative stress, and enhance the efficacy of chemotherapy and radiotherapy. It targets cancer stem cells and modulates key enzymes such as aldehyde dehydrogenase (ALDH) and O6-methylguanine-DNA methyltransferase (MGMT), thereby increasing tumor sensitivity to agents such as gemcitabine and temozolomide. In glioblastoma, disulfiram also inhibits polo-like kinase 1 and proteasome activity, promoting apoptosis. In HIV therapy, disulfiram contributes to the “shock-and-kill” strategy by reactivating latent viral reservoirs without significant immune activation. In COVID-19, it may inhibit viral proteases (Mpro, PLpro) and reduce neutrophil extracellular trap (NET) formation, potentially mitigating disease severity. Observational studies suggest a reduced risk of infection and symptom development among disulfiram users. Beyond these areas, disulfiram has demonstrated in vitro activity against a broad spectrum of pathogens, including Borrelia burgdorferi, vancomycin-resistant bacteria, hepatitis C virus, and various parasites. It has also been explored as an adjunct in the treatment of cocaine dependence. Although most findings remain preclinical, the breadth of disulfiram’s biological activity supports continued investigation into its therapeutic potential across diverse medical domains.