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World J Gastroenterol. Nov 7, 2018; 24(41): 4635-4642
Published online Nov 7, 2018. doi: 10.3748/wjg.v24.i41.4635
Concept of histone deacetylases in cancer: Reflections on esophageal carcinogenesis and treatment
Dimitrios Schizas, Aikaterini Mastoraki, Leon Naar, Eleftherios Spartalis, Diamantis I Tsilimigras, Georgia-Sofia Karachaliou, George Bagias, Dimitrios Moris
Dimitrios Schizas, Aikaterini Mastoraki, Diamantis I Tsilimigras, 1st Department of Surgery, Laikon General Hospital, National and Kapodistrian University of Athens, Athens 11527, Greece
Leon Naar, 4th Department of Surgery, Attikon University Hospital, National and Kapodistrian University of Athens, Athens 12462, Greece
Eleftherios Spartalis, Georgia-Sofia Karachaliou, Laboratory of Experimental Surgery and Surgical Research, National and Kapodistrian University of Athens, Athens 11527, Greece
George Bagias, Department of General, Visceral and Transplant Surgery, University Hospital Essen, Essen 45141, Germany
Dimitrios Moris, Department of Surgery, Duke University Medical Center, Durham, NC 27710, United States
Author contributions: All authors equally contributed to this paper with conception and design of the study, literature review and analysis, drafting and critical revision and editing, and final approval of the final version.
Conflict-of-interest statement: No potential conflicts of interest. No financial support.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dimitrios Moris, MD, MSc, PhD, Academic Fellow, Academic Research, Doctor, Research Fellow, Surgeon, Department of Surgery, Duke University Medical Center, Duke University, 2301 Erwin Rd, Durham, NC 27710, United States. dimitrios.moris@duke.edu
Telephone: +1-216-5716614 Fax: +1-919-3347890
Received: August 7, 2018
Peer-review started: August 7, 2018
First decision: August 30, 2018
Revised: September 2, 2018
Accepted: October 5, 2018
Article in press: October 5, 2018
Published online: November 7, 2018
Processing time: 92 Days and 12.8 Hours
Abstract

Esophageal cancer (EC) presents a high mortality rate, mainly due to its aggressive nature. Squamous cell carcinoma is the most common histological type worldwide, though, a continuous increase in esophageal adenocarcinomas has been noted in the past decades. Common risk factors associated with EC include smoking, alcohol consumption, gastroesophageal reflux disease, Barrett’s esophagus and obesity. In an effort to overcome chemotherapy resistance in oncology, it was discovered that histone acetylation/deacetylation equilibrium is altered in carcinogenesis, leading to changes in chromatin structure and altering expression of genes important in the cell cycle, differentiation and apoptosis. Based on this knowledge, histone acetylation was addressed as a potential novel chemotherapy drug target to repress cancer cell proliferation. There are four classes of histone deacetylases (HDACs) inhibitors with a variety of different mechanisms of actions that render them possible anti-cancer drugs. They arrest the cell cycle, inhibit differentiation and angiogenesis and induce apoptosis. They do not necessarily act on histone proteins, since they can also exert indirect anti-cancer effects, by modifying various cellular proteins. In addition, HDACs have also been associated with increased chemotherapy resistance. Based on the literature, HDACs have been associated with EC, with surveys revealing that increased expression of certain HDACs correlates with advanced TNM stages, tumor grade, metastatic potential and decreased 5-year overall and disease-free survival. The aim of this survey is to elucidate the molecular identity and mechanism of action of HDAC inhibitors as well as verify their potential utility as anti-cancer agents in esophageal cancer.

Keywords: Esophageal cancer; Histone deacatylases; Inhibitors; Drugs

Core tip: Esophageal cancer (EC) remains one of the most lethal malignancies, mainly due to its aggressive nature. In an effort to overcome chemotherapy resistance, it was discovered that histone acetylation/deacetylation equilibrium is altered in carcinogenesis, leading to changes in chromatin structure and altering expression of genes important in the cell cycle, differentiation and apoptosis. Therefore, histone acetylation was addressed as a potential novel chemotherapy drug target. Based on the literature, histone deacetylases (HDACs) have been associated with EC, with surveys elucidating that increased expression of certain HDACs correlates with advanced TNM stages, tumor grade, metastatic potential and decreased 5-year overall and disease-free survival.