Its possible mechanisms included a) the downregulation of transporters such as hENT1 in GEM-R cells decreased adenosine entry into cells, and adenosine accumulation in the extracellular environment stimulated increase of glycolysis in tumor cells to generate energy through the AMPK pathway [35, 36], b) our previous study [51] indicated that c-Myc and HIF-1α, two key regulators of glucose transport and metabolism, were more highly expressed in GEM-resistant pancreatic cancer cells than GEM-sensitive cells, confirming the crosstalk between glycolysis and chemoresistance. This evidence concerns the gene HIF1A and pancreatic neoplasm.