Universität zu Köln

Pfarr, N. and Merkelbach-Bruse, S. (2021). Homologous recombination repair deficiency as a predictive biomarker Basic mechanisms and detection methods. Pathologe, 42 (4). S. 391 - 399. HEIDELBERG: SPRINGER HEIDELBERG. ISSN 1432-1963

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Abstract

Background DNA double-strand breaks may evoke cell death or cancer. Cells have developed two fundamentally different mechanisms of DNA double-strand repair: the accurate mechanism of homologous recombination repair and the error-prone nonhomologous end joining. The deficiency of homologous recombination repair (HRD) is a frequent feature of several solid tumor entities and is associated with sensitivity to poly(ADP-ribose) polymerase (PARP) inhibitor therapy. Objectives Among other biomarkers, HRD testing provides an opportunity to guide PARP inhibitor therapy in solid tumors, but the basic principles are complex and the use and benefits of the different methodologies remain controversial. Knowledge of the underlying mechanisms at the molecular level will advance our understanding and will pave the way to introduce the testing of new biomarkers. Methods An overview of the fundamental mechanisms of DNA repair is provided. Important terms like HRR, HRD, and BRCAness are defined, and analysis methods are described, especially with regard to their integration in molecular pathology routine diagnostics. Results Currently, at least testing of the BRCA mutation status and genomic instability using a composite HRD score should be implemented in laboratories to identify subgroups of patients who might benefit from PARP inhibitor therapies. A broad range of testing methods is available with pros and cons for introduction in the clinical setting. They have to be validated carefully to reliably inform treatment selection. Conclusions Biomarkers to identify current homologous recombination deficiency status are needed to predict the benefit from PARP inhibitors and stratify their use in clinical management. Besides commercial assays, different tests might be used for the analysis of HRD. The application depends, among other things, on the local situation and has to be extensively validated.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Pfarr, N. UNSPECIFIED UNSPECIFIED UNSPECIFIED Merkelbach-Bruse, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-570641
DOI:	10.1007/s00292-021-00950-9
Journal or Publication Title:	Pathologe
Volume:	42
Number:	4
Page Range:	S. 391 - 399
Date:	2021
Publisher:	SPRINGER HEIDELBERG
Place of Publication:	HEIDELBERG
ISSN:	1432-1963
Language:	German
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DNA-REPAIR; BREAST-CANCER; DAMAGE; SENSITIVITY; HALLMARKS; BRCA1 Multiple languages Pathology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/57064