SMO and cancer: This is due to the predominant dependence of certain types of human cancers on canonical HH signaling (sensitivity; basal cell carcinoma [19, 20], medulloblastoma [16, 21]), or alternatively circumvention of SMO as a therapeutic target in preclinical models and clinically (intrinsic resistance [9, 14, 16-18, 22]) due to activation of GLI by alternate non-canonical, oncogenic signaling pathways [7, 22, 27, 33-35].