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Targeting Akt in Hepatocellular Carcinoma and Its Tumor Microenvironment.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2021 Feb 11; Vol. 22 (4). Date of Electronic Publication: 2021 Feb 11. - Publication Year :
- 2021
-
Abstract
- 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.
- Subjects :
- Aminopyridines therapeutic use
Carcinoma, Hepatocellular enzymology
Heterocyclic Compounds, 3-Ring therapeutic use
Humans
Imidazoles therapeutic use
Liver Neoplasms enzymology
Proto-Oncogene Proteins c-akt metabolism
Pyrimidines therapeutic use
Pyrroles therapeutic use
Carcinoma, Hepatocellular drug therapy
Drug Delivery Systems
Liver Neoplasms drug therapy
Protein Kinase Inhibitors therapeutic use
Proto-Oncogene Proteins c-akt antagonists & inhibitors
Tumor Microenvironment
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 22
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 33670268
- Full Text :
- https://doi.org/10.3390/ijms22041794