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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 14, 2016; 22(2): 823-832
Published online Jan 14, 2016. doi: 10.3748/wjg.v22.i2.823
Targeting Wnt/β-catenin pathway in hepatocellular carcinoma treatment
Valery Vilchez, Lilia Turcios, Francesc Marti, Roberto Gedaly
Valery Vilchez, Lilia Turcios, Francesc Marti, Roberto Gedaly, Department of Surgery, Division of Transplantation, College of Medicine, University of Kentucky, Lexington, KY 40536-0284, United States
Author contributions: Vilchez V, Turcios L, Marti F and Gedaly R contributed equally in developing the concept, writing and correcting this manuscript.
Conflict-of-interest statement: Authors declare no conflict of interest for this article.
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: Roberto Gedaly, MD, Department of Surgery, Division of Transplantation, College of Medicine, University of Kentucky, Lexington, KY 40536-0284, United States. rgeda2@uky.edu
Telephone: +1-859-3234661 Fax: +1-859-2573644
Received: October 27, 2015
Peer-review started: October 31, 2015
First decision: November 13, 2015
Revised: December 5, 2015
Accepted: December 19, 2015
Article in press: December 21, 2015
Published online: January 14, 2016
Abstract

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death worldwide. Liver cancer is generally related to hepatitis B or C infection and cirrhosis. Usually, patients with HCC are asymptomatic and are diagnosed at late stages when surgical treatment is no longer suitable. Limited treatment options for patients with advanced HCC are a major concern. Therefore, there is an urge for finding novel therapies to treat HCC. Liver cancer is highly heterogeneous and involved deregulation of several signaling pathways. Wnt/β-catenin pathway is frequently upregulated in HCC and it is implicated in maintenance of tumor initiating cells, drug resistance, tumor progression, and metastasis. A great effort in developing selective drugs to target components of the β-catenin pathway with anticancer activity is underway but only a few of them have reached phase I clinical trials. We aim to review the role of β-catenin pathway on hepatocarcinogenesis and liver cancer stem cell maintenance. We also evaluated the use of small molecules targeting the Wnt/β-catenin pathway with potential application for treatment of HCC.

Keywords: Hepatocellular carcinoma, Wnt/β-catenin pathway, Liver cancer stem cells, Molecular therapy

Core tip: Several signaling pathways have been described to be deregulated in hepatocellular carcinoma (HCC). There are limited treatment options currently available in advanced liver cancer. Wnt/β-catenin pathway is frequently upregulated and has emerged as an alternative target in HCC. Our group has studied the role of β-catenin inhibition alone and in combination in HCC treatment. In this review we summarized the existing literature on the importance of Wnt/β-catenin pathway on hepatocarcinogenesis, tumor progression, relationship with liver stem cells and cancer therapeutics.