Unraveling the Dual Role of Voriconazole as an Antifungal Agent and Precursor to Squamous Cell Carcinoma

Abstract

Voriconazole, a potent triazole antifungal medication, is extensively used to treat serious fungal infections in immunocompromised patients. Despite its efficacy, recent findings suggest a potential link between long-term voriconazole therapy and the development of squamous cell carcinoma (SCC). This review examines the dual role of voriconazole, emphasizing both its therapeutic benefits and carcinogenic risks. The pharmacodynamics of voriconazole involve the inhibition of ergosterol synthesis, crucial to fungal cell integrity. However, its metabolites, such as voriconazole-N-oxide, have been implicated in phototoxic reactions that lead to DNA damage and tumor formation. This is particularly significant in patients with prolonged drug exposure, such as organ transplant recipients, where increased SCC incidence has been observed. Clinical evidence and molecular studies suggest that voriconazole may disrupt key cellular pathways like the Hedgehog pathway, affecting epidermal differentiation and increasing cancer risk. Given these concerns, the necessity for careful therapeutic monitoring and patient education about potential risks is discussed. Alternative antifungal therapies and protective measures against phototoxic effects are also recommended as strategies to mitigate SCC risk. Future research should focus on understanding the mechanisms of voriconazole-induced carcinogenesis and refining patient management protocols. This review highlights the need for a balanced approach to voriconazole therapy, weighing its antifungal benefits against the risks of adverse dermatological outcomes.