This strongly argues against canonical HH signaling activity in these cells and is similar to other reports showing that SMO inhibitors are mainly effective in medulloblastoma of the SHH subgroup (36) and in basal cell carcinoma that most frequently are driven by PTCH mutations (37), whereas they are of no benefit in e.g. pancreatic cancer or lung cell cancer, in which SHH overexpression was thought to be responsible for HH signaling activity in the tumors [for review see (38, 39)]. The gene discussed is SHH; the disease is medulloblastoma.