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RAD52 as a Potential Target for Synthetic Lethality-Based Anticancer Therapies

Alterations in DNA repair systems play a key role in the induction and progression of cancer. Tumor-specific defects in DNA repair mechanisms and activation of alternative repair routes create the opportunity to employ a phenomenon called “synthetic lethality” to eliminate cancer cells. Targeting th...

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Autores principales: Toma, Monika, Sullivan-Reed, Katherine, Śliwiński, Tomasz, Skorski, Tomasz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6827130/
https://www.ncbi.nlm.nih.gov/pubmed/31615159
http://dx.doi.org/10.3390/cancers11101561
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author Toma, Monika
Sullivan-Reed, Katherine
Śliwiński, Tomasz
Skorski, Tomasz
author_facet Toma, Monika
Sullivan-Reed, Katherine
Śliwiński, Tomasz
Skorski, Tomasz
author_sort Toma, Monika
collection PubMed
description Alterations in DNA repair systems play a key role in the induction and progression of cancer. Tumor-specific defects in DNA repair mechanisms and activation of alternative repair routes create the opportunity to employ a phenomenon called “synthetic lethality” to eliminate cancer cells. Targeting the backup pathways may amplify endogenous and drug-induced DNA damage and lead to specific eradication of cancer cells. So far, the synthetic lethal interaction between BRCA1/2 and PARP1 has been successfully applied as an anticancer treatment. Although PARP1 constitutes a promising target in the treatment of tumors harboring deficiencies in BRCA1/2—mediated homologous recombination (HR), some tumor cells survive, resulting in disease relapse. It has been suggested that alternative RAD52-mediated HR can protect BRCA1/2-deficient cells from the accumulation of DNA damage and the synthetic lethal effect of PARPi. Thus, simultaneous inhibition of RAD52 and PARP1 might result in a robust dual synthetic lethality, effectively eradicating BRCA1/2-deficient tumor cells. In this review, we will discuss the role of RAD52 and its potential application in synthetic lethality-based anticancer therapies.
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spelling pubmed-68271302019-11-18 RAD52 as a Potential Target for Synthetic Lethality-Based Anticancer Therapies Toma, Monika Sullivan-Reed, Katherine Śliwiński, Tomasz Skorski, Tomasz Cancers (Basel) Review Alterations in DNA repair systems play a key role in the induction and progression of cancer. Tumor-specific defects in DNA repair mechanisms and activation of alternative repair routes create the opportunity to employ a phenomenon called “synthetic lethality” to eliminate cancer cells. Targeting the backup pathways may amplify endogenous and drug-induced DNA damage and lead to specific eradication of cancer cells. So far, the synthetic lethal interaction between BRCA1/2 and PARP1 has been successfully applied as an anticancer treatment. Although PARP1 constitutes a promising target in the treatment of tumors harboring deficiencies in BRCA1/2—mediated homologous recombination (HR), some tumor cells survive, resulting in disease relapse. It has been suggested that alternative RAD52-mediated HR can protect BRCA1/2-deficient cells from the accumulation of DNA damage and the synthetic lethal effect of PARPi. Thus, simultaneous inhibition of RAD52 and PARP1 might result in a robust dual synthetic lethality, effectively eradicating BRCA1/2-deficient tumor cells. In this review, we will discuss the role of RAD52 and its potential application in synthetic lethality-based anticancer therapies. MDPI 2019-10-14 /pmc/articles/PMC6827130/ /pubmed/31615159 http://dx.doi.org/10.3390/cancers11101561 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Toma, Monika
Sullivan-Reed, Katherine
Śliwiński, Tomasz
Skorski, Tomasz
RAD52 as a Potential Target for Synthetic Lethality-Based Anticancer Therapies
title RAD52 as a Potential Target for Synthetic Lethality-Based Anticancer Therapies
title_full RAD52 as a Potential Target for Synthetic Lethality-Based Anticancer Therapies
title_fullStr RAD52 as a Potential Target for Synthetic Lethality-Based Anticancer Therapies
title_full_unstemmed RAD52 as a Potential Target for Synthetic Lethality-Based Anticancer Therapies
title_short RAD52 as a Potential Target for Synthetic Lethality-Based Anticancer Therapies
title_sort rad52 as a potential target for synthetic lethality-based anticancer therapies
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6827130/
https://www.ncbi.nlm.nih.gov/pubmed/31615159
http://dx.doi.org/10.3390/cancers11101561
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