Repurposing itraconazole in clinical dermato-oncology beyond conventional antifungal use: a review

Itraconazole, a broad-spectrum triazole antifungal agent, is known to inhibit the Sonic Hedgehog (SHH) signalling cascade-a pivotal oncogenic pathway in basal cell carcinoma (BCC). Unlike conventional SHH pathway inhibitors such as vismodegib and sonidegib, which exert their effect via direct binding to the transmembrane protein Smoothened (SMO), itraconazole impedes intracellular SMO trafficking, thereby attenuating downstream pathway activation. Given the rising global demand for accessible and cost-effective therapeutic alternatives, this review aims to critically appraise the emerging oncologic applications of itraconazole in dermato-oncology. A systematic literature search was conducted using PubMed, Scopus and Google Scholar databases, incorporating keywords such as "itraconazole," "basal cell carcinoma," "Sonic Hedgehog pathway," and "angiogenesis inhibition." Clinical trials, case series, and preclinical studies were analysed to assess efficacy endpoints, and safety profiles. Its primary application in basal cell carcinoma, where SHH dysregulation is a key driver, has shown promising results. Off-label evidence further supports its role in vascular neoplasms such as infantile hemangiomas, where angiogenesis is central to pathogenesis. Despite encouraging preliminary evidence, further investigation through randomized controlled trials is warranted to optimize dosage regimens, define therapeutic windows, and explore synergistic potential with existing oncologic agents. The repositioning of itraconazole exemplifies the expanding interface between dermatology and oncology and highlights the promise of drug repurposing in cutaneous malignancies.