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Targeting Akt in Hepatocellular Carcinoma and Its Tumor Microenvironment

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related deaths worldwide, and its incidence is rising. HCC develops almost exclusively on the background of chronic liver inflammation, which can be caused by chronic alcohol consumption, viral hepatitis, or an unhealthy diet....

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Autores principales: Mroweh, Mariam, Roth, Gaël, Decaens, Thomas, Marche, Patrice N., Lerat, Hervé, Macek Jílková, Zuzana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917860/
https://www.ncbi.nlm.nih.gov/pubmed/33670268
http://dx.doi.org/10.3390/ijms22041794
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author Mroweh, Mariam
Roth, Gaël
Decaens, Thomas
Marche, Patrice N.
Lerat, Hervé
Macek Jílková, Zuzana
author_facet Mroweh, Mariam
Roth, Gaël
Decaens, Thomas
Marche, Patrice N.
Lerat, Hervé
Macek Jílková, Zuzana
author_sort Mroweh, Mariam
collection PubMed
description Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related deaths worldwide, and its incidence is rising. HCC develops almost exclusively on the background of chronic liver inflammation, which can be caused by chronic alcohol consumption, viral hepatitis, or an unhealthy diet. The key role of chronic inflammation in the process of hepatocarcinogenesis, including in the deregulation of innate and adaptive immune responses, has been demonstrated. The inhibition of Akt (also known as Protein Kinase B) directly affects cancer cells, but this therapeutic strategy also exhibits indirect anti-tumor activity mediated by the modulation of the tumor microenvironment, as demonstrated by using Akt inhibitors AZD5363, MK-2206, or ARQ 092. Moreover, the isoforms of Akt converge and diverge in their designated roles, but the currently available Akt inhibitors fail to display an isoform specificity. Thus, selective Akt inhibition needs to be better explored in the context of HCC and its possible combination with immunotherapy. This review presents a compact overview of the current knowledge concerning the role of Akt in HCC and the effect of Akt inhibition on the HCC and liver tumor microenvironment.
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spelling pubmed-79178602021-03-02 Targeting Akt in Hepatocellular Carcinoma and Its Tumor Microenvironment Mroweh, Mariam Roth, Gaël Decaens, Thomas Marche, Patrice N. Lerat, Hervé Macek Jílková, Zuzana Int J Mol Sci Review Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related deaths worldwide, and its incidence is rising. HCC develops almost exclusively on the background of chronic liver inflammation, which can be caused by chronic alcohol consumption, viral hepatitis, or an unhealthy diet. The key role of chronic inflammation in the process of hepatocarcinogenesis, including in the deregulation of innate and adaptive immune responses, has been demonstrated. The inhibition of Akt (also known as Protein Kinase B) directly affects cancer cells, but this therapeutic strategy also exhibits indirect anti-tumor activity mediated by the modulation of the tumor microenvironment, as demonstrated by using Akt inhibitors AZD5363, MK-2206, or ARQ 092. Moreover, the isoforms of Akt converge and diverge in their designated roles, but the currently available Akt inhibitors fail to display an isoform specificity. Thus, selective Akt inhibition needs to be better explored in the context of HCC and its possible combination with immunotherapy. This review presents a compact overview of the current knowledge concerning the role of Akt in HCC and the effect of Akt inhibition on the HCC and liver tumor microenvironment. MDPI 2021-02-11 /pmc/articles/PMC7917860/ /pubmed/33670268 http://dx.doi.org/10.3390/ijms22041794 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Mroweh, Mariam
Roth, Gaël
Decaens, Thomas
Marche, Patrice N.
Lerat, Hervé
Macek Jílková, Zuzana
Targeting Akt in Hepatocellular Carcinoma and Its Tumor Microenvironment
title Targeting Akt in Hepatocellular Carcinoma and Its Tumor Microenvironment
title_full Targeting Akt in Hepatocellular Carcinoma and Its Tumor Microenvironment
title_fullStr Targeting Akt in Hepatocellular Carcinoma and Its Tumor Microenvironment
title_full_unstemmed Targeting Akt in Hepatocellular Carcinoma and Its Tumor Microenvironment
title_short Targeting Akt in Hepatocellular Carcinoma and Its Tumor Microenvironment
title_sort targeting akt in hepatocellular carcinoma and its tumor microenvironment
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917860/
https://www.ncbi.nlm.nih.gov/pubmed/33670268
http://dx.doi.org/10.3390/ijms22041794
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