In the context of striking chemo-radiotherapy resistance of pancreatic cancers and the fundamental role of RLIP76 as an important mercapturic acid pathway transporter that is essential for survival and therapy resistance in cancers, we investigated the role of RLIP76 in regulating the critical signaling proteins involved in relaying the inputs from multiple upstream survival pathways and mechanisms contributing to chemo-radiotherapy resistance in pancreatic cancer. This evidence concerns the gene RALBP1 and familial pancreatic carcinoma.