Pre-clinical Study of Itraconazole in Mice for the Chemotherapy of Basal Cell Carcinomas

Basal cell carcinoma (BCC) is the most common human cancer that affects approximately 3 million Americans each year. The hedgehog signaling pathway is the primary driver of BCC carcinogenesis. Basal Cell Nevus Syndrome (BCNS) is a rare autosomal inherited disorder where patients inherit mutations in genes leading to increased, uncontrolled hedgehog signaling. The goal of this study was to repurpose a commonly used antifungal drug, itraconazole, for the treatment of BCCs due to the recent identification of itraconazole as an inhibitor of the hedgehog pathway. Common administration of itraconazole is oral; however, patients with BCNS would be unable to receive oral itraconazole for lifetime therapy due to adverse effects. We developed a topical itraconazole cream for BCC treatment/prevention. We applied itraconazole or control creams onto murine BCCs to determine the effect of itraconazole on HH pathway target genes (Gli1 mRNA, QPCR) and to correlate anti-HH activity with drug concentrations in tumor (as measured by LC-MS). Itraconazole cream reduced Gli1 (50% decrease, P=0.0418) and had low plasma levels when compared to oral itraconazole indicating better drug safety. Mice treated with Itraconazole cream showed a reduction in tumor growth and a reduction in Gli1 expression indicating drug efficacy. In conclusion, topical itraconazole cream is a potential anti-BCC treatment.