Human Equilibrative Nucleoside Transporter 1 (hENT1) in Pancreatic Adenocarcinoma: Towards Individualized Treatment Decisions

Abstract: Pancreatic cancer is one of the most lethal cancers, where curative surgical resections are rare and less than 5% of patients experience long-term survival. Despite numerous clinical trials, improvements in the systemic treatment of this disease have been limited. Gemcitabine, a nucleoside analogue, is still considered the standard of care chemotherapy for most patients in the advanced disease setting. To exert its cytotoxic effects, gemcitabine must enter cells via nucleoside transporters, most notably human equilibrative nucleoside transporter 1 (hENT1). Increasingly strong evidence suggests hENT1 is a prognostic biomarker in gemcitabine-treated pancreatic cancer, and may well be a predictive biomarker of gemcitabine efficacy. In this review, we synthesize the literature surrounding hENT1 in pancreatic cancer, identify the key outstanding questions, and suggest strategies to prospectively evaluate the clinical utility of hENT1 in future clinical studies.