The canonical Hh pathway unambiguously displays the Hh-PTCH-SMO-GLI route, and its aberrant activation has been shown in a variety of cancers, including basal cell carcinoma, gliomas, medulloblastoma, leukemias, breast cancer, lung cancer, and pancreatic cancer, etc. To date, two SMO inhibitors (LDE-225/Sonidegib and GDC-0449/Vismodegib) and one GLI2 inhibitor (arsenic trioxide, ATO) have received the US Food and Drug Administration (FDA) approval for treating basal cell carcinoma and acute promyelocytic leukemia, respectively [48]. The gene discussed is GLI2; the disease is familial pancreatic carcinoma.