TGFB1 and familial pancreatic carcinoma: Furthermore, clinical trials on colorectal, ovarian and pancreatic cancer failed to demonstrate therapeutic efficacy of SMO inhibition [13], which may at least in part be due to SMO-independent activation of oncogenic GLI activity by for instance TGFβ, RAS, PI3K/AKT/S6K or genetic deletion of the GLI repressor SUFU (reviewed in [7, 49]).