SMO and cancer: However, despite an initial clinical response, a number of drug-resistant Smo mutations were observed in patients also in recent clinical trials.7, 8, 9 Further, some clinical trials have failed so far,10, 11, 12, 13 due to poor pharmacokinetics, low selectivity on cancer stem cells (CSCs), and the presence of bystander co-regulatory mechanisms of the Hh pathway.