We found for the first time that HIF-2α dictates the susceptibility of pancreatic cancer cell lines, Panc-1 and AsPC-1, to TRAIL, by transcriptionally regulating survivin, an anti-apoptotic molecule, and that survivin may be a promising target to augment the therapeutic efficacy of DR-targeting anti-cancer therapy. This evidence concerns the gene TNFSF10 and familial pancreatic carcinoma.