Universität zu Köln

Wagener-Ryczek, Svenja, Merkelbach-Bruse, Sabine and Siemanowski, Janna (2021). Biomarkers for Homologous Recombination Deficiency in Cancer. J. Pers. Med., 11 (7). BASEL: MDPI. ISSN 2075-4426

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Abstract

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 BRCA 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Wagener-Ryczek, Svenja UNSPECIFIED UNSPECIFIED UNSPECIFIED Merkelbach-Bruse, Sabine UNSPECIFIED UNSPECIFIED UNSPECIFIED Siemanowski, Janna UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-563604
DOI:	10.3390/jpm11070612
Journal or Publication Title:	J. Pers. Med.
Volume:	11
Number:	7
Date:	2021
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	2075-4426
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DNA-REPAIR; CLINICAL ASSAYS; BREAST-CANCER; DAMAGE; RECOMMENDATIONS; MAINTENANCE; SENSITIVITY; MECHANISMS; INHIBITORS; BRCA1 Multiple languages Health Care Sciences & Services; Medicine, General & Internal Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/56360