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Role of Akt Activation in PARP Inhibitor Resistance in Cancer
Poly(ADP-ribose) polymerase (PARP) inhibitors have recently been introduced in the therapy of several types of cancers not responding to conventional treatments. However, de novo and acquired PARP inhibitor resistance is a significant limiting factor in the clinical therapy, and the underlying mecha...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139751/ https://www.ncbi.nlm.nih.gov/pubmed/32106627 http://dx.doi.org/10.3390/cancers12030532 |
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author | Gallyas, Ferenc Sumegi, Balazs Szabo, Csaba |
author_facet | Gallyas, Ferenc Sumegi, Balazs Szabo, Csaba |
author_sort | Gallyas, Ferenc |
collection | PubMed |
description | Poly(ADP-ribose) polymerase (PARP) inhibitors have recently been introduced in the therapy of several types of cancers not responding to conventional treatments. However, de novo and acquired PARP inhibitor resistance is a significant limiting factor in the clinical therapy, and the underlying mechanisms are not fully understood. Activity of the cytoprotective phosphatidylinositol-3 kinase (PI3K)-Akt pathway is often increased in human cancer that could result from mutation, expressional change, or amplification of upstream growth-related factor signaling elements or elements of the Akt pathway itself. However, PARP-inhibitor-induced activation of the cytoprotective PI3K-Akt pathway is overlooked, although it likely contributes to the development of PARP inhibitor resistance. Here, we briefly summarize the biological role of the PI3K-Akt pathway. Next, we overview the significance of the PARP-Akt interplay in shock, inflammation, cardiac and cerebral reperfusion, and cancer. We also discuss a recently discovered molecular mechanism that explains how PARP inhibition induces Akt activation and may account for apoptosis resistance and mitochondrial protection in oxidative stress and in cancer. |
format | Online Article Text |
id | pubmed-7139751 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-71397512020-04-10 Role of Akt Activation in PARP Inhibitor Resistance in Cancer Gallyas, Ferenc Sumegi, Balazs Szabo, Csaba Cancers (Basel) Review Poly(ADP-ribose) polymerase (PARP) inhibitors have recently been introduced in the therapy of several types of cancers not responding to conventional treatments. However, de novo and acquired PARP inhibitor resistance is a significant limiting factor in the clinical therapy, and the underlying mechanisms are not fully understood. Activity of the cytoprotective phosphatidylinositol-3 kinase (PI3K)-Akt pathway is often increased in human cancer that could result from mutation, expressional change, or amplification of upstream growth-related factor signaling elements or elements of the Akt pathway itself. However, PARP-inhibitor-induced activation of the cytoprotective PI3K-Akt pathway is overlooked, although it likely contributes to the development of PARP inhibitor resistance. Here, we briefly summarize the biological role of the PI3K-Akt pathway. Next, we overview the significance of the PARP-Akt interplay in shock, inflammation, cardiac and cerebral reperfusion, and cancer. We also discuss a recently discovered molecular mechanism that explains how PARP inhibition induces Akt activation and may account for apoptosis resistance and mitochondrial protection in oxidative stress and in cancer. MDPI 2020-02-25 /pmc/articles/PMC7139751/ /pubmed/32106627 http://dx.doi.org/10.3390/cancers12030532 Text en © 2020 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 Gallyas, Ferenc Sumegi, Balazs Szabo, Csaba Role of Akt Activation in PARP Inhibitor Resistance in Cancer |
title | Role of Akt Activation in PARP Inhibitor Resistance in Cancer |
title_full | Role of Akt Activation in PARP Inhibitor Resistance in Cancer |
title_fullStr | Role of Akt Activation in PARP Inhibitor Resistance in Cancer |
title_full_unstemmed | Role of Akt Activation in PARP Inhibitor Resistance in Cancer |
title_short | Role of Akt Activation in PARP Inhibitor Resistance in Cancer |
title_sort | role of akt activation in parp inhibitor resistance in cancer |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139751/ https://www.ncbi.nlm.nih.gov/pubmed/32106627 http://dx.doi.org/10.3390/cancers12030532 |
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