SMO and cancer: Basal cell carcinoma (BCC) is the most common cancer in the Western world with an annual incidence of 3–4 million new cases in the US alone.1 Genetic activation of the hedgehog (HH)/GLI pathway by inactivating mutations in the patched (PTCH) gene or—more rarely—by activating mutations in the smoothened (SMO) gene represents the main driver signal in BCC pathogenesis.