Work

Repurposing Disulfiram for Cancer Therapy: Mechanistic Insights and Translational Challenges

Year: 2026

Type: article

Abstract: Disulfiram (DSF), long used as an aversive agent in alcohol dependence therapy, has recently regained attention as a promising candidate for oncological drug repurposing. After administration, DSF is rapidly reduced to diethyldithiocarbamate (DDC), which in the presence of Cu²⁺ forms the complex Cu(DDC)₂. This compound acts as a strong inducer of oxidative stress, an inhibitor of the ubiquitin–proteasome system, and a suppressor of endogenous hydrogen sulfide (H₂S) synthesis. DSF also modifies protein and non-protein thiol groups, disrupting cancer cell metabolism and promoting apoptosis. Despite robust preclinical evidence, clinical translation remains limited. Key obstacles include DSF’s rapid metabolism, insufficient availability of free copper ions in humans, and the lack of predictive biomarkers capable of identifying responsive patients. Another challenge is DSF’s low oral bioavailability, which prevents the drug from reaching tumor tissue at therapeutically effective concentrations. Consequently, current research focuses on advanced nanocarrier systems designed to protect DSF from premature degradation and ensure its controlled release within the tumor microenvironment. This review summarizes the multifaceted anticancer mechanisms of DSF and discusses biological and pharmacological factors underlying the discrepancies between experimental findings and clinical outcomes.

Source: International Journal of Molecular Sciences

DOI: 10.3390/ijms27177667

Authors: Anna Bilska-Wilkosz, Magdalena Górny, Małgorzata Iciek

Institution: Jagiellonian University

Language: English

Topic: Bioactive Compounds and Antitumor Agents

Subfield: Toxicology

Field: Pharmacology, Toxicology and Pharmaceutics

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,499