Repurposing Auranofin for Oncology and Beyond: A Brief Overview of Clinical Trials as Mono- and Combination Therapy

Auranofin (AF) is an oral gold(I) compound with a well-known pharmacological profile, currently used in the treatment of some severe forms of rheumatoid arthritis. Over the last twenty years, AF has also been repurposed as antitumor, antiviral, and antibacterial drug. In this context, this review provides an updated overview of all clinical trials investigating AF for the treatment of various pathologies, either as monotherapy or in combination with other agents. We started summarizing the rationale behind repurposing AF in oncology, including its ability to inhibit thioredoxin reductase (TrxR) and disrupt redox homeostasis, leading to selective cytotoxicity in cancer cells. Clinical data from trials across a range of tumors are reviewed, highlighting safety profiles, dosing regimens, pharmacokinetics, and observed therapeutic outcomes. Then, we discussed the synergistic effects observed when AF is combined with chemotherapeutics, targeted therapies, or immune modulators. Then, an overview concerning the trials involving AF in non-oncological setting is also provided. Despite promising preclinical results, clinical translation remains in early stages, with most trials still in phase I or II. Nevertheless, emerging evidence supports continued exploration of AF-based therapies to address unmet medical needs.