For example, the constitutive activation of intrinsic signaling pathways like Wnt‐β‐Catenin, PI3K/Akt, and NF‐κB axis affected the chemo‐resistance of patients with Pancreatic Ductal Adenocarcinoma (PDAC) by reducing the distribution and the concentration of gemcitabine at the tumor site.[52, 53] Acquired factors are generated after the therapy and induced by the drug. This evidence concerns the gene AKT1 and pancreatic ductal adenocarcinoma.