Several studies have implicated a non-canonical Hh signaling pathway in regulating HH/GLI signaling, thus substituting the necessity of upstream ligand signaling.13, 14, 15, 16 Several pathways, such as AKT,17, 18, 19 MAPK,18 RAS20 or EGFR,21, 22 can activate GLI factors in tumor cells. The gene discussed is GLI1; the disease is neoplasm.