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Insights into the Possible Molecular Mechanisms of Resistance to PARP Inhibitors
SIMPLE SUMMARY: The increasingly wide use of PARP inhibitors in breast, ovarian, pancreatic, and prostate cancers harbouring a pathogenic variant in BRCA1 or BRCA2 has highlighted the problem of resistance to therapy. This review summarises the complex interactions between PARP1, cell cycle regulati...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9179506/ https://www.ncbi.nlm.nih.gov/pubmed/35681784 http://dx.doi.org/10.3390/cancers14112804 |
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author | Piombino, Claudia Cortesi, Laura |
author_facet | Piombino, Claudia Cortesi, Laura |
author_sort | Piombino, Claudia |
collection | PubMed |
description | SIMPLE SUMMARY: The increasingly wide use of PARP inhibitors in breast, ovarian, pancreatic, and prostate cancers harbouring a pathogenic variant in BRCA1 or BRCA2 has highlighted the problem of resistance to therapy. This review summarises the complex interactions between PARP1, cell cycle regulation, response to stress replication, homologous recombination, and other DNA damage repair pathways in the setting of BRCA1/2 mutated cancers that could explain the development of primary or secondary resistance to PARP inhibitors. ABSTRACT: PARP1 enzyme plays an important role in DNA damage recognition and signalling. PARP inhibitors are approved in breast, ovarian, pancreatic, and prostate cancers harbouring a pathogenic variant in BRCA1 or BRCA2, where PARP1 inhibition results mainly in synthetic lethality in cells with impaired homologous recombination. However, the increasingly wide use of PARP inhibitors in clinical practice has highlighted the problem of resistance to therapy. Several different mechanisms of resistance have been proposed, although only the acquisition of secondary mutations in BRCA1/2 has been clinically proved. The aim of this review is to outline the key molecular findings that could explain the development of primary or secondary resistance to PARP inhibitors, analysing the complex interactions between PARP1, cell cycle regulation, PI3K/AKT signalling, response to stress replication, homologous recombination, and other DNA damage repair pathways in the setting of BRCA1/2 mutated cancers. |
format | Online Article Text |
id | pubmed-9179506 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-91795062022-06-10 Insights into the Possible Molecular Mechanisms of Resistance to PARP Inhibitors Piombino, Claudia Cortesi, Laura Cancers (Basel) Review SIMPLE SUMMARY: The increasingly wide use of PARP inhibitors in breast, ovarian, pancreatic, and prostate cancers harbouring a pathogenic variant in BRCA1 or BRCA2 has highlighted the problem of resistance to therapy. This review summarises the complex interactions between PARP1, cell cycle regulation, response to stress replication, homologous recombination, and other DNA damage repair pathways in the setting of BRCA1/2 mutated cancers that could explain the development of primary or secondary resistance to PARP inhibitors. ABSTRACT: PARP1 enzyme plays an important role in DNA damage recognition and signalling. PARP inhibitors are approved in breast, ovarian, pancreatic, and prostate cancers harbouring a pathogenic variant in BRCA1 or BRCA2, where PARP1 inhibition results mainly in synthetic lethality in cells with impaired homologous recombination. However, the increasingly wide use of PARP inhibitors in clinical practice has highlighted the problem of resistance to therapy. Several different mechanisms of resistance have been proposed, although only the acquisition of secondary mutations in BRCA1/2 has been clinically proved. The aim of this review is to outline the key molecular findings that could explain the development of primary or secondary resistance to PARP inhibitors, analysing the complex interactions between PARP1, cell cycle regulation, PI3K/AKT signalling, response to stress replication, homologous recombination, and other DNA damage repair pathways in the setting of BRCA1/2 mutated cancers. MDPI 2022-06-05 /pmc/articles/PMC9179506/ /pubmed/35681784 http://dx.doi.org/10.3390/cancers14112804 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Piombino, Claudia Cortesi, Laura Insights into the Possible Molecular Mechanisms of Resistance to PARP Inhibitors |
title | Insights into the Possible Molecular Mechanisms of Resistance to PARP Inhibitors |
title_full | Insights into the Possible Molecular Mechanisms of Resistance to PARP Inhibitors |
title_fullStr | Insights into the Possible Molecular Mechanisms of Resistance to PARP Inhibitors |
title_full_unstemmed | Insights into the Possible Molecular Mechanisms of Resistance to PARP Inhibitors |
title_short | Insights into the Possible Molecular Mechanisms of Resistance to PARP Inhibitors |
title_sort | insights into the possible molecular mechanisms of resistance to parp inhibitors |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9179506/ https://www.ncbi.nlm.nih.gov/pubmed/35681784 http://dx.doi.org/10.3390/cancers14112804 |
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