Review
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World J Gastroenterol. Feb 28, 2013; 19(8): 1173-1181
Published online Feb 28, 2013. doi: 10.3748/wjg.v19.i8.1173
Histone deacetylase inhibitors and pancreatic cancer: Are there any promising clinical trials?
Ioannis Koutsounas, Constantinos Giaginis, Stamatios Theocharis
Ioannis Koutsounas, Constantinos Giaginis, Stamatios Theocharis, Department of Forensic Medicine and Toxicology, Medical School, 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, Giaginis C and Theocharis S contributed to this paper equally.
Correspondence to: Stamatios Theocharis, MD, PhD, Pathologist, Associate Professor of the Department of Forensic Medicine and Toxicology, Medical School, University of Athens, 75, Mikras Asias Street, Goudi, GR11527 Athens, Greece. theocharis@ath.forthnet.gr
Telephone: +30-21-7462413 Fax: +30-21-7716098
Received: June 9, 2011
Revised: October 18, 2011
Accepted: August 15, 2012
Published online: February 28, 2013
Abstract

Pancreatic cancer, although not very frequent, has an exceptionally high mortality rate, making it one of the most common causes of cancer mortality in developed countries. Pancreatic cancer is difficult to diagnose, allowing few patients to have the necessary treatment at a relatively early stage. Despite a marginal benefit in survival, the overall response of pancreatic cancer to current systemic therapy continues to be poor, and new therapies are desperately needed. Histone deacetylase (HDAC) enzymes play an important role in the development and progression of cancer and HDAC inhibitors (HDACIs) have been shown to induce differentiation and cell cycle arrest, activate the extrinsic or intrinsic pathways of apoptosis, and inhibit invasion, migration and angiogenesis in different cancer cell lines. As a result of promising preclinical data, various HDACIs are being tested as either monotherapeutic agents or in combination regimens for both solid and hematological malignancies. Vorinostat was the first HDACI approved by the Food and Drug Administration for patients with cutaneous T-cell lymphoma. The use of HDACIs in clinical trials, in pretreated and relapsed patients suffering from advanced pancreatic cancer is discussed. Unfortunately, clinical data for HDACIs in patients with pancreatic cancer are inadequate, because only a few studies have included patients suffering from this type of neoplasm and the number of pancreatic cancer patients that entered HDACIs phase II/III trials, among others with advanced solid tumors, is very limited. More studies recruiting patients with pancreatic cancer remain to determine the efficiency of these therapies.

Keywords: Pancreatic cancer; Histone deacetylases; Histone deacetylase inhibitors; Clinical trials