Equilibrative nucleoside transporters (ENTs) are responsible for the uptake of a large number of nucleosides and nucleoside analogs. hENT1 is the most abundant and is widely distributed in human cells. It is the major transporter by which gemcitabine enters cells and decreased levels is an established resistance mechanism in vitro. However, high levels represent an increase in positive predictive factors for patients’ response to gemcitabine. hENT expression is, therefore, a prognostic marker for patients with resected cancer but is it also a biomarker for pancreatic cancer? This study demonstrated that hENT expression in pancreatic tissue was highly variable among individuals and that moderate to high levels of hENT was expressed in malignant pancreatic cancers but very little to any in normal pancreatic tissues. Recent published studies in our laboratory have shown that the non-toxic dietary agent, indole-3-carbinol (IC3), can modulate hENT expression in pancreatic cancer cell lines, increasing expression of this transporter and further enhancing the efficacy of gemicitabine.
Moderate to high level of expression of hENT in tumor tissues and not normal pancreatic tissues suggest that it could also be a biomarker, however larger number of samples are needed for validation. Modulation of hENT expression by I3C could prove to be an important agent for combination therapy in patients expressing low levels of hENT.
Citation Format: Beverly Lyn-Cook, Honggang Wang, Li Pang, Beverly Word. Individual variation in hENT expression in normal and malignant pancreatic tissues: The role of dietary agents in enhancing efficacy in gemcitabine treatment. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Progress and Challenges; Jun 18-21, 2012; Lake Tahoe, NV. Philadelphia (PA): AACR; Cancer Res 2012;72(12 Suppl):Abstract nr A44.