Despite the promising preclinical results on targeting Notch2 and Notch3 to overcome gemcitabine resistance, the addition of anti-Notch2/3 antibody tarextumab to gemcitabine and nab-paclitaxel worsened the PFS in metastatic pancreatic cancer patients, and contrasting with the precedent correlations, patients’ responses did not correlate with Notch3 expression [208]. This evidence concerns the gene NOTCH3 and familial pancreatic carcinoma.