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Alonso-Peña et al. Cancer Drug Resist 2019;2:680-709 Cancer
DOI: 10.20517/cdr.2019.006 Drug Resistance

Review Open Access

Pharmacogenetics of hepatocellular carcinoma and
cholangiocarcinoma

Marta Alonso-Peña , Anabel Sanchez-Martin , Paula Sanchon-Sanchez , Meraris Soto-Muñiz , Ricardo
1
1
1
1
Espinosa-Escudero , Jose J.G. Marin 1,2
1
1 Experimental Hepatology and Drug Targeting (HEVEFARM), IBSAL, University of Salamanca, Salamanca 37007, Spain.
2 Center for the Study of Liver and Gastrointestinal Diseases (CIBERehd). Carlos III National Institute of Health, Madrid 28029,
Spain.
Correspondence to: Prof. Jose J.G. Marin, Department of Physiology and Pharmacology, Campus Miguel de Unamuno E.I.D.
S-09, Salamanca 37007, Spain. E-mail: jjgmarin@usal.es
How to cite this article: Alonso-Peña M, Sanchez-Martin A, Sanchon-Sanchez P , Soto-Muñiz M, Espinosa-Escudero R, Marin
JJG. Pharmacogenetics of hepatocellular carcinoma and cholangiocarcinoma. Cancer Drug Resist 2019;2:680-709.
http://dx.doi.org/10.20517/cdr.2019.006

Received: 22 Jan 2019 First Decision: 26 Feb 2019 Revised: 18 May 2019 Accepted: 3 Jun 2019 Published: 19 Sep 2019
Science Editor: Godefridus J. Peters Copy Editor: Cai-Hong Wang Production Editor: Jing Yu

Abstract
Primary liver cancers constitute the fourth most deadly group of cancers. Their poor prognosis is due in part to
the pre-existence and/or development, often during treatment, of powerful mechanisms accounting for the poor
response of cancer cells to antitumor drugs. These include both impaired gene expression and the appearance
of spliced variants, polymorphisms and mutations, affecting the function of genes leading to the reduction in
intracellular concentrations of active agents, changes in molecular targets and survival pathways, altered tumor
microenvironment and phenotypic transition. The present review summarizes available information regarding
the role of germline and somatic mutations affecting drug transporters, enzymes involved in drug metabolism,
organelles and signaling molecules related to liver cancer chemoresistance. A more complete picture of the actual
complexity of this problem is urgently needed for carrying out further pharmacogenomic studies aimed to improve
the management of patients suffering from hepatocellular carcinoma or cholangiocarcinoma.

Keywords: Anticancer drug, chemoresistance, chemotherapy, cholangiocarcinoma, germline mutation, hepatoma,
liver cancer, somatic mutation

INTRODUCTION
Primary liver cancers (PLCs) are an important proportion of total malignant neoplasias, constituting the
fourth cause of cancer-related death worldwide. According to data from Global Cancer Observatory, there

© The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0
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