INS and neoplasm: Some of these molecular alterations found in squamous PDAC, such as inhibition of pancreatic epithelial differentiation genes (HNF4A and GATA6) [67] together with increased hypoxia [58,59,60,63,68], HIF1A, C-MYC [58,59,60] and WNT, insulin, and PI3K-AKT signaling [72], promote a metabolic rewiring of tumor cells to glycolysis.