ArticleActa dermato-venereologica2025
Possible Clinical Effects of Ketoconazole on Sorafenib-induced Hand-Foot Skin Reaction and Cytoprotection Mechanisms of Antifungal Agents against Multikinase Inhibitor-induced Keratinocyte Toxicity.
Article in Acta dermato-venereologica, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
2 citing papers in PubMed.
- Biogenic Zinc Oxide Nanoparticles for Skin Disorders: Mechanistic Insights, Translational Challenges, and Future Prospects.Biological trace element research · 2026Review
- Transforming a Roadblock into a Roadmap: Evolving HFSR Management From Adverse Event to Efficacy Biomarker.Current treatment options in oncology · 2026Review
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Authors and funding
8 authors.
Funding
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Abstract
In recent years, molecular target drugs have become integral in treating malignant tumours. Multikinase inhibitors (MKIs) have been associated with serious skin disorders, including hand-foot skin reaction (HFSR), which impair patient quality of life, often disrupting activities of daily living necessitating dose reduction or discontinuation. As the pathogenic mechanisms of these skin disorders are unknown, no effective treatments have been established. Previously, by drug repurposing using an in vitro culture system, certain azole antifungal drugs (AFDs) were identified that prevented sorafenib-induced cell death of normal human epidermal keratinocytes. In this study, topical ketoconazole demonstrated clinical improvement in hyperkeratosis and pain associated with sorafenib-induced HFSR. Investigation of the mechanism using the in vitro culture system revealed sorafenib to be particularly cytotoxic among MKIs. Annexin V and TUNEL staining revealed apoptosis was mainly involved in this cytotoxicity. Antibody arrays and western blot showed increased levels of secretion of interleukin-1 receptor antagonist and macrophage migration inhibitory factor in culture supernatants. AFDs suppressed the secretion of these cytokines and reduced apoptosis in keratinocytes. This study reveals one aspect of the pathogenesis of sorafenib-induced HFSR and demonstrates that AFDs may be an effective treatment.
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