DNA repair in cancer: emerging targets for personalized therapy

Genomic deoxyribonucleic acid (DNA) is under constant threat from endogenous and exogenous DNA damaging agents. Mammalian cells have evolved highly conserved DNA repair machinery to process DNA damage and maintain genomic integrity. Impaired DNA repair is a major driver for carcinogenesis and could...

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Main Authors: Abbotts, Rachel, Thompson, Nicola, Madhusudan, Srinivasan
Format: Article
Published: Dove Medical Press 2014
Online Access:https://eprints.nottingham.ac.uk/3023/
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author Abbotts, Rachel
Thompson, Nicola
Madhusudan, Srinivasan
author_facet Abbotts, Rachel
Thompson, Nicola
Madhusudan, Srinivasan
author_sort Abbotts, Rachel
building Nottingham Research Data Repository
collection Online Access
description Genomic deoxyribonucleic acid (DNA) is under constant threat from endogenous and exogenous DNA damaging agents. Mammalian cells have evolved highly conserved DNA repair machinery to process DNA damage and maintain genomic integrity. Impaired DNA repair is a major driver for carcinogenesis and could promote aggressive cancer biology. Interestingly, in established tumors, DNA repair activity is required to counteract oxidative DNA damage that is prevalent in the tumor microenvironment. Emerging clinical data provide compelling evidence that overexpression of DNA repair factors may have prognostic and predictive significance in patients. More recently, DNA repair inhibition has emerged as a promising target for anticancer therapy. Synthetic lethality exploits intergene relationships where the loss of function of either of two related genes is nonlethal, but loss of both causes cell death. Exploiting this approach by targeting DNA repair has emerged as a promising strategy for personalized cancer therapy. In the current review, we focus on recent advances with a particular focus on synthetic lethality targeting in cancer.
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spelling nottingham-30232020-05-04T20:15:16Z https://eprints.nottingham.ac.uk/3023/ DNA repair in cancer: emerging targets for personalized therapy Abbotts, Rachel Thompson, Nicola Madhusudan, Srinivasan Genomic deoxyribonucleic acid (DNA) is under constant threat from endogenous and exogenous DNA damaging agents. Mammalian cells have evolved highly conserved DNA repair machinery to process DNA damage and maintain genomic integrity. Impaired DNA repair is a major driver for carcinogenesis and could promote aggressive cancer biology. Interestingly, in established tumors, DNA repair activity is required to counteract oxidative DNA damage that is prevalent in the tumor microenvironment. Emerging clinical data provide compelling evidence that overexpression of DNA repair factors may have prognostic and predictive significance in patients. More recently, DNA repair inhibition has emerged as a promising target for anticancer therapy. Synthetic lethality exploits intergene relationships where the loss of function of either of two related genes is nonlethal, but loss of both causes cell death. Exploiting this approach by targeting DNA repair has emerged as a promising strategy for personalized cancer therapy. In the current review, we focus on recent advances with a particular focus on synthetic lethality targeting in cancer. Dove Medical Press 2014-02 Article PeerReviewed Abbotts, Rachel, Thompson, Nicola and Madhusudan, Srinivasan (2014) DNA repair in cancer: emerging targets for personalized therapy. Breast Cancer: Targets and Therapy, 2014 (6). pp. 77-92. ISSN 1179-1314 http://www.dovepress.com/dna-repair-in-cancer-emerging-targets-for-personalized-therapy-a15867 doi:10.2147/CMAR.S50497 doi:10.2147/CMAR.S50497
spellingShingle Abbotts, Rachel
Thompson, Nicola
Madhusudan, Srinivasan
DNA repair in cancer: emerging targets for personalized therapy
title DNA repair in cancer: emerging targets for personalized therapy
title_full DNA repair in cancer: emerging targets for personalized therapy
title_fullStr DNA repair in cancer: emerging targets for personalized therapy
title_full_unstemmed DNA repair in cancer: emerging targets for personalized therapy
title_short DNA repair in cancer: emerging targets for personalized therapy
title_sort dna repair in cancer: emerging targets for personalized therapy
url https://eprints.nottingham.ac.uk/3023/
https://eprints.nottingham.ac.uk/3023/
https://eprints.nottingham.ac.uk/3023/