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Genetic aberrations in DNA repair pathways: a cornerstone of precision oncology in prostate cancer
Over the past years, several studies have demonstrated that defects in DNA damage response and repair (DDR) genes are present in a significant proportion of patients with prostate cancer. These alterations, particularly mutations in BRCA2, are known to be associated with an increased risk of develop...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851123/ https://www.ncbi.nlm.nih.gov/pubmed/33106584 http://dx.doi.org/10.1038/s41416-020-01114-x |
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author | Lozano, Rebeca Castro, Elena Aragón, Isabel M. Cendón, Ylenia Cattrini, Carlo López-Casas, Pedro P. Olmos, David |
author_facet | Lozano, Rebeca Castro, Elena Aragón, Isabel M. Cendón, Ylenia Cattrini, Carlo López-Casas, Pedro P. Olmos, David |
author_sort | Lozano, Rebeca |
collection | PubMed |
description | Over the past years, several studies have demonstrated that defects in DNA damage response and repair (DDR) genes are present in a significant proportion of patients with prostate cancer. These alterations, particularly mutations in BRCA2, are known to be associated with an increased risk of developing prostate cancer and more aggressive forms of the disease. There is growing evidence that certain DDR gene aberrations confer sensitivity to poly-(ADP ribose) polymerase inhibitors and/or platinum chemotherapy, while other defects might identify cases that are more likely to benefit from immune checkpoint inhibition. The potential prognostic impact and relevance for treatment selection together with the decreasing costs and broader accessibility to next-generation sequencing have already resulted in the increased frequency of genetic profiling of prostate tumours. Remarkably, almost half of all DDR genetic defects can occur in the germline, and prostate cancer patients identified as mutation carriers, as well as their families, will require appropriate genetic counselling. In this review, we summarise the current knowledge regarding the biology and clinical implications of DDR defects in prostate cancer, and outline how this evidence is prompting a change in the treatment landscape of the disease. |
format | Online Article Text |
id | pubmed-7851123 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-78511232021-02-08 Genetic aberrations in DNA repair pathways: a cornerstone of precision oncology in prostate cancer Lozano, Rebeca Castro, Elena Aragón, Isabel M. Cendón, Ylenia Cattrini, Carlo López-Casas, Pedro P. Olmos, David Br J Cancer Review Article Over the past years, several studies have demonstrated that defects in DNA damage response and repair (DDR) genes are present in a significant proportion of patients with prostate cancer. These alterations, particularly mutations in BRCA2, are known to be associated with an increased risk of developing prostate cancer and more aggressive forms of the disease. There is growing evidence that certain DDR gene aberrations confer sensitivity to poly-(ADP ribose) polymerase inhibitors and/or platinum chemotherapy, while other defects might identify cases that are more likely to benefit from immune checkpoint inhibition. The potential prognostic impact and relevance for treatment selection together with the decreasing costs and broader accessibility to next-generation sequencing have already resulted in the increased frequency of genetic profiling of prostate tumours. Remarkably, almost half of all DDR genetic defects can occur in the germline, and prostate cancer patients identified as mutation carriers, as well as their families, will require appropriate genetic counselling. In this review, we summarise the current knowledge regarding the biology and clinical implications of DDR defects in prostate cancer, and outline how this evidence is prompting a change in the treatment landscape of the disease. Nature Publishing Group UK 2020-10-27 2021-02-02 /pmc/articles/PMC7851123/ /pubmed/33106584 http://dx.doi.org/10.1038/s41416-020-01114-x Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Review Article Lozano, Rebeca Castro, Elena Aragón, Isabel M. Cendón, Ylenia Cattrini, Carlo López-Casas, Pedro P. Olmos, David Genetic aberrations in DNA repair pathways: a cornerstone of precision oncology in prostate cancer |
title | Genetic aberrations in DNA repair pathways: a cornerstone of precision oncology in prostate cancer |
title_full | Genetic aberrations in DNA repair pathways: a cornerstone of precision oncology in prostate cancer |
title_fullStr | Genetic aberrations in DNA repair pathways: a cornerstone of precision oncology in prostate cancer |
title_full_unstemmed | Genetic aberrations in DNA repair pathways: a cornerstone of precision oncology in prostate cancer |
title_short | Genetic aberrations in DNA repair pathways: a cornerstone of precision oncology in prostate cancer |
title_sort | genetic aberrations in dna repair pathways: a cornerstone of precision oncology in prostate cancer |
topic | Review Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851123/ https://www.ncbi.nlm.nih.gov/pubmed/33106584 http://dx.doi.org/10.1038/s41416-020-01114-x |
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