These results indicate that FTO and NEDD4 are novel regulators of PTEN expression and gemcitabine chemosensitivity in PDAC, and that targeting the FTO/NEDD4/PTEN/PI3K/AKT axis may be a promising strategy to overcome gemcitabine resistance in pancreatic cancer (Fig. 7). This evidence concerns the gene NEDD4 and familial pancreatic carcinoma.