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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....
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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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. |
format | Online Article Text |
id | pubmed-7917860 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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