Universität zu Köln

Dietlein, Felix, Thelen, Lisa and Reinhardt, H. Christian (2014). Cancer-specific defects in DNA repair pathways as targets for personalized therapeutic approaches. Trends Genet., 30 (8). S. 326 - 340. LONDON: ELSEVIER SCIENCE LONDON. ISSN 1362-4555

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Abstract

Defects in DNA repair pathways enable cancer cells to accumulate genomic alterations that contribute to their aggressive phenotype. However, tumors rely on residual DNA repair capacities to survive the damage induced by genotoxic stress. This dichotomy might explain why only isolated DNA repair pathways are inactivated in cancer cells. Accordingly, synergism has been observed between DNA-damaging drugs and targeted inhibitors of DNA repair. DNA repair pathways are generally thought of as mutually exclusive mechanistic units handling different types of lesions in distinct cell cycle phases. Recent preclinical studies, however, provide strong evidence that multifunctional DNA repair hubs, which are involved in multiple conventional DNA repair pathways, are frequently altered in cancer. We therefore propose that targeted anticancer therapies should not only exploit synthetic lethal interactions between two single genes but also consider alterations in DNA repair hubs. Such a network-based approach considerably increases the opportunities for targeting DNA repair-defective tumors.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Dietlein, Felix UNSPECIFIED UNSPECIFIED UNSPECIFIED Thelen, Lisa UNSPECIFIED UNSPECIFIED UNSPECIFIED Reinhardt, H. Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-432946
DOI:	10.1016/j.tig.2014.06.003
Journal or Publication Title:	Trends Genet.
Volume:	30
Number:	8
Page Range:	S. 326 - 340
Date:	2014
Publisher:	ELSEVIER SCIENCE LONDON
Place of Publication:	LONDON
ISSN:	1362-4555
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language STRAND BREAK REPAIR; CHRONIC LYMPHOCYTIC-LEUKEMIA; NUCLEOTIDE-EXCISION-REPAIR; IDENTIFIES RECURRENT MUTATIONS; SACCHAROMYCES-CEREVISIAE MSH2; ONCOGENE-INDUCED SENESCENCE; SYNTHETIC DOSAGE LETHALITY; CROSS-LINK REPAIR; OF-THE-ART; HOMOLOGOUS RECOMBINATION Multiple languages Genetics & Heredity Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/43294