SHH and neoplasm: It has been shown that tumour-derived sonic hedgehog (Shh) activates smoothened (SMO) in fibroblasts, which activates the fibroblasts and consequently promotes PDAC desmoplasia.60 When Hh signalling was inhibited in CAFs in a PDAC mouse model using the drug IPI-926, the tumours became transiently vascularised and delivery of the chemotherapeutic agent gemcitabine was enhanced, increasing mouse survival.