Background: Repurposing antifungal drugs in cancer therapy has attracted unprecedented attention in both preclinical and clinical research due to specific advantages, such as safety, high-cost effectiveness and time savings compared with cancer drug discovery. The surprising and encouraging efficacy of antifungal drugs in cancer therapy, mechanistically, is attributed to the overlapping targets or molecular pathways between fungal and cancer pathogenesis. Advancements in omics, informatics and analytical technology have led to the discovery of increasing "off-site" targets from antifungal drugs involved in cancerogenesis, such as smoothened (D477G) inhibition from itraconazole in basal cell carcinoma.
Aim of review: This review illustrates several antifungal drugs repurposed for cancer therapy and reveals the underlying mechanism based on their original target and "off-site" target. Furthermore, the challenges and perspectives for the future development and clinical applications of antifungal drugs for cancer therapy are also discussed, providing a refresh understanding of drug repurposing.
Key scientific concepts of review: This review may provide a basic understanding of repurposed antifungal drugs for clinical cancer management, thereby helping antifungal drugs broaden new indications and promote clinical translation.
Keywords: Antifungal drugs; Cancer therapy; Drug discovery; Drug repurposing; Drug targets.
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