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Molecular Bases of Drug Resistance in Hepatocellular Carcinoma

1
Experimental Hepatology and Drug Targeting (HEVEFARM) Group, University of Salamanca, IBSAL, 37007 Salamanca, Spain
2
Center for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, 28029 Madrid, Spain
*
Authors to whom correspondence should be addressed.
Cancers 2020, 12(6), 1663; https://doi.org/10.3390/cancers12061663
Received: 4 June 2020 / Revised: 19 June 2020 / Accepted: 20 June 2020 / Published: 23 June 2020
(This article belongs to the Special Issue Resistance to Therapy in Liver and Gastrointestinal Tumors)
The poor outcome of patients with non-surgically removable advanced hepatocellular carcinoma (HCC), the most frequent type of primary liver cancer, is mainly due to the high refractoriness of this aggressive tumor to classical chemotherapy. Novel pharmacological approaches based on the use of inhibitors of tyrosine kinases (TKIs), mainly sorafenib and regorafenib, have provided only a modest prolongation of the overall survival in these HCC patients. The present review is an update of the available information regarding our understanding of the molecular bases of mechanisms of chemoresistance (MOC) with a significant impact on the response of HCC to existing pharmacological tools, which include classical chemotherapeutic agents, TKIs and novel immune-sensitizing strategies. Many of the more than one hundred genes involved in seven MOC have been identified as potential biomarkers to predict the failure of treatment, as well as druggable targets to develop novel strategies aimed at increasing the sensitivity of HCC to pharmacological treatments. View Full-Text
Keywords: apoptosis; cancer stem cell; DNA repair; epithelial-mesenchymal transition; liver cancer; metabolism; multidrug resistance; refractoriness; transport; tumor environment apoptosis; cancer stem cell; DNA repair; epithelial-mesenchymal transition; liver cancer; metabolism; multidrug resistance; refractoriness; transport; tumor environment
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MDPI and ACS Style

Marin, J.J.; Macias, R.I.; Monte, M.J.; Romero, M.R.; Asensio, M.; Sanchez-Martin, A.; Cives-Losada, C.; Temprano, A.G.; Espinosa-Escudero, R.; Reviejo, M.; Bohorquez, L.H.; Briz, O. Molecular Bases of Drug Resistance in Hepatocellular Carcinoma. Cancers 2020, 12, 1663.

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