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Briz et al. Hepatoma Res 2017;3:22-6 Hepatoma Research
DOI: 10.20517/2394-5079.2016.22
www.hrjournal.net
Review Open Access

Further understanding of mechanisms

involved in liver cancer chemoresistance

Oscar Briz, Maria J. Perez, Jose J. G. Marin
Department of Physiology and Pharmacology, University of Salamanca, 37007 Salamanca, Spain

Correspondence to: Dr. Jose J. G. Marin, Department of Physiology and Pharmacology, Experimental Hepatology and Drug Targeting (HEVEFARM),
CIBERehd, IBSAL, University of Salamanca, Campus Miguel de Unamuno E.I.D. S-09, 37007 Salamanca, Spain. E-mail: jjgmarin@usal.es

How to cite this article: Briz O, Perez MJ, Marin JJG. Further understanding of mechanisms involved in liver cancer chemoresistance. Hepatoma
Res 2017;3:22-6.
ABSTRACT

Article history: An important limitation for the success of chemotherapy in the treatment of primary liver cancer
Received: 15-06-2016 (hepatocellular carcinoma, hepatoblastoma and cholangiocarcinoma) is the marked efficacy of
Accepted: 19-12-2016 mechanisms of chemoresistance (MOC). These have been previously classified into five groups
Published: 19-01-2017 depending on whether they result in: a reduced drug uptake or enhanced drug export (MOC-1); poor
intracellular activation of prodrugs or higher inactivation of active drugs (MOC-2); changes in
Key words: the molecular targets that impairs the action of the drug by increasing the activity of the metabolic
Chemotherapy, route to be inhibited or stimulating alternative routes (MOC-3); ability of tumor cells to repair
cholangiocarcinoma, drug-induced modifications in the target molecule, usually DNA (MOC-4); and the activation or
hepatoblastoma, inhibition of intracellular signaling pathways that lead to a change in the balance between pro-
hepatocellular carcinoma, and anti-apoptotic factors favoring tumor cell survival (MOC-5). Nevertheless, novel information
tumor environment, appeared over the last few years has recommended to consider two additional groups, MOC-6
epithelial-mesenchymal transition and MOC-7, based on changes in tumor microenvironment, mainly hypoxia and acidity, and
epithelial-mesenchymal transition, respectively. These contribute to the defensive armamentaria
developed or enhanced in liver cancer cells to resist the pharmacological attack, which accounts
for a negligible beneficial effect of commonly used antitumor drugs and only a modest response
to novel targeted therapies based on tyrosine kinase inhibitors, such as sorafenib. Therefore,
further advances are urgently needed to better understand the molecular and cellular bases of
the chemoresistant barrier and help scientists in this field to develop new tools able to overcome
cancer cell defenses.

[1]
INTRODUCTION previously been classified into five groups depending
on whether they result in: reduced drug uptake or
An important limitation for the success of chemotherapy enhanced drug export (MOC-1); poor intracellular
in the treatment of primary liver cancer [hepatocellular activation of pro-drugs or higher inactivation of active
carcinoma (HCC), hepatoblastoma (HPB) or drugs (MOC-2); changes in the molecular targets that
cholangiocarcinoma (CCA)] is the marked efficacy of impairs the action of the drug by increasing the activity
mechanisms of chemoresistance (MOC) that have of the target route to be inhibited, or the appearance

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