Review
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World J Gastroenterol. Feb 14, 2013; 19(6): 813-828
Published online Feb 14, 2013. doi: 10.3748/wjg.v19.i6.813
Current evidence for histone deacetylase inhibitors in pancreatic cancer
Ioannis Koutsounas, Constantinos Giaginis, Efstratios Patsouris, Stamatios Theocharis
Ioannis Koutsounas, Constantinos Giaginis, Efstratios Patsouris, Stamatios Theocharis, First Department of Pathology, Medical School, National and Kapodistrian University of Athens, GR-11527 Athens, Greece
Constantinos Giaginis, Department of Food Science and Nutrition, University of the Aegean, GR-81400 Lemnos, Greece
Author contributions: Koutsounas I collected and analyzed literature data and wrote the paper; Giaginis C collected and analyzed literature data; Patsouris E collected funds for the study; and Theocharis S designed the study and analyzed literature data.
Correspondence to: Stamatios Theocharis, MD, PhD, Pathologist, Associate Professor of the Department of Pathology, Medical School, National and Kapodistrian University of Athens, GR-11527 Athens, Greece. theocharis@ath.forthnet.gr
Telephone: +30-21-7462413 Fax: +30-21-7716098
Received: June 9, 2011
Revised: October 18, 2011
Accepted: January 5, 2013
Published online: February 14, 2013
Abstract

Pancreatic cancer is one of the most aggressive human cancers, with more than 200 000 deaths worldwide every year. Despite recent efforts, conventional treatment approaches, such as surgery and classic chemotherapy, have only slightly improved patient outcomes. More effective and well-tolerated therapies are required to reverse the current poor prognosis of this type of neoplasm. Among new agents, histone deacetylase inhibitors (HDACIs) are now being tested. HDACIs have multiple biological effects related to acetylation of histones and many non-histone proteins that are involved in regulation of gene expression, apoptosis, cell cycle progression and angiogenesis. HDACIs induce cell cycle arrest and can activate the extrinsic and intrinsic pathways of apoptosis in different cancer cell lines. In the present review, the main mechanisms by which HDACIs act in pancreatic cancer cells in vitro, as well as their antiproliferative effects in animal models are presented. HDACIs constitute a promising treatment for pancreatic cancer with encouraging anti-tumor effects, at well-tolerated doses.

Keywords: Pancreatic cancer; Histone deacetylases; Histone deacetylase inhibitors; Experimental studies