However, despite the good efficacy observed in a subset of patients, results obtained with Vismodegib have been disappointing for two main reasons: (1) the drug is not effective in patients carrying mutations localized downstream of SMO [51,52]; (2) Even in patients that showed good response, tumor cells eventually become drug resistant, due to novel SMO mutations or activation of compensatory mechanisms that restore the function of the downstream effectors [38,53,54,55]. Here, SMO is linked to neoplasm.