The emerging data from clinical trials with GDC-0449 show both the benefits and possible pitfalls of a pure SMO antagonist; a clear tumor response in Hh driven tumors such as basal cell carcinoma and medulloblastoma [34], [55], [56], and the occurrence of a drug induced resistance caused by mutations in the Smo locus [34], [55]. Here, SMO is linked to neoplasm.