Given the potential clinical benefits seen with high-dose itraconazole in the CRPC setting that were associated with Hedgehog pathway inhibition in skin biopsies, and the relatively mild toxicity profiles in early-phase trials of more potent SMO inhibitors (intolerable grade-2 adverse events including dysgeusia, muscle spasms, and alopecia are notable), there has been increased interest in evaluating the clinical utility of these inhibitors in men with prostate cancer. The gene discussed is SMO; the disease is prostate cancer.