Review
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Pharmacol. Mar 9, 2015; 4(1): 96-116
Published online Mar 9, 2015. doi: 10.5497/wjp.v4.i1.96
Hepatocellular carcinoma and multidrug resistance: Past, present and new challenges for therapy improvement
María L Cuestas, José R Oubiña, Verónica L Mathet
María L Cuestas, José R Oubiña, Verónica L Mathet, Instituto de Investigaciones en Microbiología y Parasitología Médica (IMPaM, UBA-CONICET), Facultad de Medicina, Universidad de Buenos Aires-Consejo Nacional de Investigaciones Científicas y Técnicas, Paraguay 2155, Buenos Aires, Argentina
Author contributions: Cuestas ML, Oubiña JR and Mathet VL contributed to this paper.
Conflict-of-interest: The authors declare no competing financial interests.
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: Verónica L Mathet, PhD, Instituto de Investigaciones en Microbiología y Parasitología Médica (IMPaM, UBA-CONICET), Facultad de Medicina, Universidad de Buenos Aires-Consejo Nacional de Investigaciones Científicas y Técnicas, piso 11 (C1121ABG), Paraguay 2155, Buenos Aires, Argentina. vmathet@yahoo.com
Telephone: +54-11-59509500 Fax: +54-11-49642554
Received: July 29, 2014
Peer-review started: July 29, 2014
First decision: September 18, 2014
Revised: November 13, 2014
Accepted: November 27, 2014
Article in press: December 1, 2014
Published online: March 9, 2015
Processing time: 226 Days and 15.7 Hours
Abstract

Hepatocellular carcinoma (HCC) is the most frequent form of liver cancer and the third most common cause of cancer-related death in the world. The main risk factor worldwide for this type of malignancy is chronic hepatitis caused by hepatitis B virus and hepatitis C virus infections. Advances in early detection and treatment have improved life expectancy of patients with HCC. However, this disorder remains as a disease with poor prognosis. In fact, epidemiological studies have revealed that there is an 8-mo median survival rate in patients, approximately 20% of whom survive one year while only 5% remain alive after three years. Additionally, HCC is particularly difficult to treat because of its high recurrence rate, and its resistance to conventional chemotherapy is due, among other mechanisms, to several members of the ATP-Binding Cassette protein family involved in drug transport being overexpressed. Fortunately, there is evidence that these patients may benefit from alternative molecular-targeted therapies. This manuscript intends to provide further insight into the etiology and molecular mechanisms related to HCC development and the latest therapeutic approaches to treat this malignancy. The development of effective delivery systems of antitumor drugs able to target the liver parenchyma is also assessed. Finally, the prospects in the development of more efficient drug therapies to overcome multidrug resistance are also examined.

Keywords: Hepatocellular carcinoma; Therapy; Multidrug resistance; Drug delivery systems; Liver targeting

Core tip: Hepatocellular carcinoma (HCC) is the most frequent malignancy of the liver. Despite the advances in early detection and treatment, this disorder still has a poor prognosis. This manuscript reviews the ongoing knowledge regarding the etiology and molecular mechanisms implicated in HCC development and the therapeutic strategies for the management of this malignancy. Finally, the development of effective delivery systems of antitumor drugs able to target the liver parenchyma as well as the prospects in the development of a more efficient drug therapy to overcome multidrug resistance are also examined.