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. 2011 Nov 15;3(11):153-64.
doi: 10.4251/wjgo.v3.i11.153.

Molecular predictors of gemcitabine response in pancreatic cancer

Ioannis A Voutsadakis  1
Affiliations

Molecular predictors of gemcitabine response in pancreatic cancer

Ioannis A Voutsadakis. World J Gastrointest Oncol. .

Abstract

Gemcitabine is one of the most used anti-neoplastic drugs with documented activity in almost all major localizations of cancer. In pancreatic cancer treatment, gemcitabine occupies a prominent place as a first line chemotherapy, partly because of the paucity of other efficacious chemotherapy options. In fact, only a minority of pancreatic cancer patients display a response or even stability of disease with the drug. There are currently no clinically applicable means of predicting which patient will derive a clinical benefit from gemcitabine although several proposed markers have been studied. These markers are proteins involved in drug up-take, activation and catabolism or proteins that define the ability of the cell to undergo apoptosis in response to the drug. Several of these markers are reviewed in this paper. We also briefly discuss the possible role of stem cells in drug resistance to gemcitabine.

Keywords: Akt kinase; Chemotherapy; Drug resistance; Gemcitabine; Metabolism; Nuclear factor-κB; Pancreatic cancer.

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Figures

Figure 1
Figure 1
Intracellular transport and metabolism of gemcitabine. For abbreviations see text. Enzymatic transformations are represented by arrows and inhibitions by т type joining.
Figure 2
Figure 2
Phosphatidylinositol-3 kinase/akt/nuclear factor-κB-related pathways involved in gemcitabine resistance. Arrows denote up-regulation or activation and т type joinings denote down-regulation or inhibition. NGF: Nerve growth factor; ILK: Integrin-linked kinase; CEACAM6: Carcinoembryonic antigen cell adhesion molecule 6; FAK: Focal adhesion kinase; PI3K: Phosphatidylinositol-3 kinase; NF-κB: Nuclear factor-κB.
Figure 3
Figure 3
Simplified representation of the web that regulates epithelial to mesenchymal transition or the reverse process mesenchymal to epithelial transition. Epithelial to mesenchymal transition (EMT) promotion is associated with gemcitabine resistance. Arrows denote up-regulation or activation and т type joinings denote down-regulation or inhibition. MET: Mesenchymal to epithelial transition; ZEB: Zinc finger E-box binding; TGFβ: Transforming growth factor β; NF-κB: Nuclear factor-κB.
See this image and copyright information in PMC

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