In this paper, we demonstrate that treatment of pancreatic cancer cells with gemcitabine significantly induces APE/ref-1 protein expression and endonuclease activity, and that the suppression of APE/ref-1 activity by antisense oligonucleotides produces a large increase in chemosensitivity in gemcitabine-treated Panc-1 cells. This evidence concerns the gene APEX1 and familial pancreatic carcinoma.