itraconazole + vismodegib

**Itraconazole + vismodegib** is a combination of two small molecule drugs used off-label for the treatment of advanced or difficult-to-treat basal cell carcinoma (BCC). Both drugs are **hedgehog pathway inhibitors**, but they bind to different sites on the smoothened (SMO) protein, allowing for potential additive or synergistic inhibition of the pathway. Vismodegib is an orally administered SMO inhibitor approved for advanced BCC, while itraconazole, primarily an antifungal agent, has also shown hedgehog pathway inhibition properties and modest activity against BCC in clinical settings[1][2][3][4]. The rationale for combination therapy is to maximize pathway inhibition, potentially reduce or delay resistance, and allow lower doses of vismodegib, thereby reducing toxicity. Preliminary and anecdotal clinical cases suggest that combined lower-dose vismodegib and itraconazole can yield significant responses in advanced BCC, sometimes with less severe adverse effects compared to full-dose vismodegib monotherapy[1][4].