We recently demonstrated that RAGE has a unique role in pancreatic tumorigenesis and drug resistance.18, 19, 20, 21, 22 Knock down or knock out of RAGE in vitro or in vivo attenuates oncogenic KRAS-driven pancreatic tumor progression19 and reverses the resistance to multiple drugs.20,21 We demonstrated that the mechanism by which this occurs is partly involved in inflammatory response-associated metabolic changes19,22,23 and cell death-associated autophagy.20,21,24,25 Thus, targeting RAGE represents a novel approach for pancreatic cancer therapy. This evidence concerns the gene KRAS and familial pancreatic carcinoma.