Table of Contents
ISRN Oncology
Volume 2011, Article ID 936893, 5 pages
Review Article

Novel Strategy with Gemcitabine for Advanced Pancreatic Cancer

1Department of Surgical Oncology, Gifu University Graduate School of Medicine, Yanagido, 1-1 Yanagido, Gifu 501-1194, Japan
2Department of Surgery, Ibi Welfare Hospital, Ibi, Gifu 501-0619, Japan

Received 16 February 2011; Accepted 8 April 2011

Academic Editor: A. R. Mackay

Copyright © 2011 Shuji Komori et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


5-fluorouracil (5-FU) is widely used in chemotherapy for gastric and colorectal cancer, but gemcitabine (GEM), and not 5-FU, is approved as a standard drug for use in pancreatic cancer. Interindividual variation in the enzyme activity of the GEM metabolic pathway can affect the extent of GEM metabolism and the efficacy of GEM chemotherapy. Human equilibrative nucleoside transporter 1 (hENT1) is recognized as a major transporter of GEM into cells. In addition, a factor that activates hENT1 is the inhibition of thymidylate synthase (TS), one of the 5-FU metabolic enzymes; TS inhibition mediates depleting intracellular nucleotide pools, resulting in the activation of the salvage pathway mediated through hENT1. In this paper, the role of 5-FU in GEM-based chemotherapy for pancreatic cancer is discussed with special emphasis on enzymes involved in the 5-FU and GEM metabolic pathways and in the correlation between GEM responsiveness and the expression of 5-FU and GEM metabolic enzymes.