Biomarkers for Homologous Recombination Deficiency in Cancer
DNA double-strand breaks foster tumorigenesis and cell death. Two distinct mechanisms can be activated by the cell for DNA repair: the accurate mechanism of homologous recombination repair or the error-prone non-homologous end joining. Homologous Recombination Deficiency (HRD) is associated with sen...
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doaj-9bfca5b62d474371b799b417260e7f2a2021-07-23T13:49:23ZengMDPI AGJournal of Personalized Medicine2075-44262021-06-011161261210.3390/jpm11070612Biomarkers for Homologous Recombination Deficiency in CancerSvenja Wagener-Ryczek0Sabine Merkelbach-Bruse1Janna Siemanowski2Institute of Pathology, University Hospital Cologne, D-50924 Cologne, GermanyInstitute of Pathology, University Hospital Cologne, D-50924 Cologne, GermanyInstitute of Pathology, University Hospital Cologne, D-50924 Cologne, GermanyDNA double-strand breaks foster tumorigenesis and cell death. Two distinct mechanisms can be activated by the cell for DNA repair: the accurate mechanism of homologous recombination repair or the error-prone non-homologous end joining. Homologous Recombination Deficiency (HRD) is associated with sensitivity towards PARP inhibitors (PARPi) and its determination is used as a biomarker for therapy decision making. Nevertheless, the biology of HRD is rather complex and the application, as well as the benefit of the different HRD biomarker assays, is controversial. Acquiring knowledge of the underlying molecular mechanisms is the main prerequisite for integration of new biomarker tests. This study presents an overview of the major DNA repair mechanisms and defines the concepts of HRR, HRD and BRCAness. Moreover, currently available biomarker assays are described and discussed with respect to their application for routine clinical diagnostics. Since patient stratification for efficient PARP inhibitor therapy requires determination of the <i>BRCA</i> mutation status and genomic instability, both should be established comprehensively. For this purpose, a broad spectrum of distinct assays to determine such combined HRD scores is already available. Nevertheless, all tests require careful validation using clinical samples to meet the criteria for their establishment in clinical testing.https://www.mdpi.com/2075-4426/11/7/612DNA double-strand breakBRCAhomologous recombinationHRD scoreBRCAnessPARPi |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Svenja Wagener-Ryczek Sabine Merkelbach-Bruse Janna Siemanowski |
spellingShingle |
Svenja Wagener-Ryczek Sabine Merkelbach-Bruse Janna Siemanowski Biomarkers for Homologous Recombination Deficiency in Cancer Journal of Personalized Medicine DNA double-strand break BRCA homologous recombination HRD score BRCAness PARPi |
author_facet |
Svenja Wagener-Ryczek Sabine Merkelbach-Bruse Janna Siemanowski |
author_sort |
Svenja Wagener-Ryczek |
title |
Biomarkers for Homologous Recombination Deficiency in Cancer |
title_short |
Biomarkers for Homologous Recombination Deficiency in Cancer |
title_full |
Biomarkers for Homologous Recombination Deficiency in Cancer |
title_fullStr |
Biomarkers for Homologous Recombination Deficiency in Cancer |
title_full_unstemmed |
Biomarkers for Homologous Recombination Deficiency in Cancer |
title_sort |
biomarkers for homologous recombination deficiency in cancer |
publisher |
MDPI AG |
series |
Journal of Personalized Medicine |
issn |
2075-4426 |
publishDate |
2021-06-01 |
description |
DNA double-strand breaks foster tumorigenesis and cell death. Two distinct mechanisms can be activated by the cell for DNA repair: the accurate mechanism of homologous recombination repair or the error-prone non-homologous end joining. Homologous Recombination Deficiency (HRD) is associated with sensitivity towards PARP inhibitors (PARPi) and its determination is used as a biomarker for therapy decision making. Nevertheless, the biology of HRD is rather complex and the application, as well as the benefit of the different HRD biomarker assays, is controversial. Acquiring knowledge of the underlying molecular mechanisms is the main prerequisite for integration of new biomarker tests. This study presents an overview of the major DNA repair mechanisms and defines the concepts of HRR, HRD and BRCAness. Moreover, currently available biomarker assays are described and discussed with respect to their application for routine clinical diagnostics. Since patient stratification for efficient PARP inhibitor therapy requires determination of the <i>BRCA</i> mutation status and genomic instability, both should be established comprehensively. For this purpose, a broad spectrum of distinct assays to determine such combined HRD scores is already available. Nevertheless, all tests require careful validation using clinical samples to meet the criteria for their establishment in clinical testing. |
topic |
DNA double-strand break BRCA homologous recombination HRD score BRCAness PARPi |
url |
https://www.mdpi.com/2075-4426/11/7/612 |
work_keys_str_mv |
AT svenjawagenerryczek biomarkersforhomologousrecombinationdeficiencyincancer AT sabinemerkelbachbruse biomarkersforhomologousrecombinationdeficiencyincancer AT jannasiemanowski biomarkersforhomologousrecombinationdeficiencyincancer |
_version_ |
1721287592251490304 |