Review
Copyright ©2010 Baishideng. All rights reserved.
World J Hepatol. Mar 27, 2010; 2(3): 114-126
Published online Mar 27, 2010. doi: 10.4254/wjh.v2.i3.114
Hepatic cancer stem cells and drug resistance: Relevance in targeted therapies for hepatocellular carcinoma
Caecilia HC Sukowati, Natalia Rosso, Lory S Crocè, Claudio Tiribelli
Caecilia HC Sukowati, Natalia Rosso, Claudio Tiribelli, Centro Studi Fegato, AREA Science Park Basovizza, Trieste 34012, Italy
Lory S Crocè, Claudio Tiribelli, Centro Clinico Studi Fegato, University of Trieste, Trieste 34012, Italy
Author contributions: Sukowati CHC conducted the extensive literature search and wrote the review; Rosso N and Crocè LS read, revised the text with the addition of references and approved the text; Tiribelli C read, edited and approved the text.
Supported by a Grant from the Italian Liver Foundation
Correspondence to: Caecilia HC Sukowati, PhD, Centro Studi Fegato, Bld Q AREA Science Park Basovizza, Trieste 34012, Italy. c.sukovati@csf.units.it
Telephone: +39-040-3757840 Fax: +39-040-3757832
Received: August 15, 2009
Revised: January 15, 2010
Accepted: January 22, 2010
Published online: March 27, 2010
Abstract

Hepatocellular carcinoma (HCC) is one of most common malignancies in the world. Systemic treatments for HCC, particularly for advanced stages, are limited by the drug resistance phenomenon which ultimately leads to therapy failure. Recent studies have indicated an association between drug resistance and the existence of the cancer stem cells (CSCs) as tumor initiating cells. The CSCs are resistant to conventional chemotherapies and might be related to the mechanisms of the ATP Binding Cassette (ABC) transporters and alterations in the CSCs signaling pathways. Therefore, to contribute to the development of new HCC treatments, further information on the characterization of CSCs, the modulation of the ABC transporters expression and function and the signaling pathway involved in the self renewal, initiation and maintenance of the cancer are required. The combination of transporters modulators/inhibitors with molecular targeted therapies may be a potent strategy to block the tumoral progression. This review summarizes the association of CSCs, drug resistance, ABC transporters activities and changes in signaling pathways as a guide for future molecular therapy for HCC.

Keywords: Hepatocellular carcinoma; Liver; Cancer stem cells; Drug resistance; Hepatocellular carcinoma therapy