Affiliation:
1. Department of Gastroenterology, Vila Nova de Gaia/Espinho Hospital Center, Vila Nova de Gaia, Portugal | Department
of Biomedicine, Unit of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal
2. Department of Gastroenterology, Vila Nova de Gaia/Espinho Hospital Center, Vila Nova de Gaia, Portugal
Abstract
Background:
Molecular therapy with sorafenib remains the mainstay for advancedstage
hepatocellular carcinoma. Notwithstanding, treatment efficacy is low, with few patients obtaining
long-lasting benefits due to the high chemoresistance rate.
Objective:
To perform, for the first time, an overview of the literature concerning the role of adenosine
triphosphate-binding cassette (ABC) transporters in sorafenib therapy for hepatocellular carcinoma.
Methods:
Three online databases (PubMed, Web of Science, and Scopus) were searched, from inception
to October 2020. Study selection, analysis, and data collection were independently performed
by two authors.
Results:
The search yielded 224 results; 29 were selected for inclusion. Most studies were pre-clinical,
using HCC cell lines; three used human samples. Studies highlight the effect of sorafenib in decreasing
ABC transporters expression. Conversely, it is described the role of ABC transporters, particularly
multidrug resistance protein 1 (MDR-1), multidrug resistance-associated proteins 1 and 2
(MRP-1 and MRP-2) and ABC subfamily G member 2 (ABCG2) in sorafenib pharmacokinetics
and pharmacodynamics, being key resistance factors. Combination therapy with naturally available
or synthetic compounds that modulate ABC transporters may revert sorafenib resistance by increasing
absorption and intracellular concentration.
Conclusion:
A deeper understanding of ABC transporters’ mechanisms may provide guidance for
developing innovative approaches for hepatocellular carcinoma. Further studies are warranted to
translate the current knowledge into practice and paving the way to individualized therapy.
Publisher
Bentham Science Publishers Ltd.
Subject
Clinical Biochemistry,Drug Discovery,Pharmacology,Molecular Medicine
Cited by
7 articles.
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