CNT1 deletion in mice was not detrimental to mouse fertility or survival due to putative compensatory mechanisms but rendered the frontline chemotherapeutic nucleoside drug gemcitabine (dFdC) less effective in a syngeneic mouse model of pancreatic cancer by increasing the urinary clearance of the drug, leading to accelerated mortality. Here, SLC28A1 is linked to familial pancreatic carcinoma.