The addition of PDE5 inhibitors to multiple existing treatment regimens, including doxorubicin, mitomycin C, gemcitabine, cisplatin and paclitaxel, significantly enhanced chemotherapy lethality by stimulating the extrinsic apoptosis pathway via CD95 and by promoting autophagy through RIP-1 (receptor interacting protein 1) in bladder and pancreatic cancer cell lines [156]. Here, RIPK1 is linked to familial pancreatic carcinoma.