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DNA repair as a shared hallmark in cancer and ageing

Increasing evidence demonstrates that DNA damage and genome instability play a crucial role in ageing. Mammalian cells have developed a wide range of complex and well‐orchestrated DNA repair pathways to respond to and resolve many different types of DNA lesions that occur from exogenous and endogeno...

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Detalles Bibliográficos
Autores principales: Clarke, Thomas L., Mostoslavsky, Raul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9490147/
https://www.ncbi.nlm.nih.gov/pubmed/35834102
http://dx.doi.org/10.1002/1878-0261.13285
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author Clarke, Thomas L.
Mostoslavsky, Raul
author_facet Clarke, Thomas L.
Mostoslavsky, Raul
author_sort Clarke, Thomas L.
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description Increasing evidence demonstrates that DNA damage and genome instability play a crucial role in ageing. Mammalian cells have developed a wide range of complex and well‐orchestrated DNA repair pathways to respond to and resolve many different types of DNA lesions that occur from exogenous and endogenous sources. Defects in these repair pathways lead to accelerated or premature ageing syndromes and increase the likelihood of cancer development. Understanding the fundamental mechanisms of DNA repair will help develop novel strategies to treat ageing‐related diseases. Here, we revisit the processes involved in DNA damage repair and how these can contribute to diseases, including ageing and cancer. We also review recent mechanistic insights into DNA repair and discuss how these insights are being used to develop novel therapeutic strategies for treating human disease. We discuss the use of PARP inhibitors in the clinic for the treatment of breast and ovarian cancer and the challenges associated with acquired drug resistance. Finally, we discuss how DNA repair pathway‐targeted therapeutics are moving beyond PARP inhibition in the search for ever more innovative and efficacious cancer therapies.
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spelling pubmed-94901472022-09-30 DNA repair as a shared hallmark in cancer and ageing Clarke, Thomas L. Mostoslavsky, Raul Mol Oncol Reviews Increasing evidence demonstrates that DNA damage and genome instability play a crucial role in ageing. Mammalian cells have developed a wide range of complex and well‐orchestrated DNA repair pathways to respond to and resolve many different types of DNA lesions that occur from exogenous and endogenous sources. Defects in these repair pathways lead to accelerated or premature ageing syndromes and increase the likelihood of cancer development. Understanding the fundamental mechanisms of DNA repair will help develop novel strategies to treat ageing‐related diseases. Here, we revisit the processes involved in DNA damage repair and how these can contribute to diseases, including ageing and cancer. We also review recent mechanistic insights into DNA repair and discuss how these insights are being used to develop novel therapeutic strategies for treating human disease. We discuss the use of PARP inhibitors in the clinic for the treatment of breast and ovarian cancer and the challenges associated with acquired drug resistance. Finally, we discuss how DNA repair pathway‐targeted therapeutics are moving beyond PARP inhibition in the search for ever more innovative and efficacious cancer therapies. John Wiley and Sons Inc. 2022-07-28 2022-09 /pmc/articles/PMC9490147/ /pubmed/35834102 http://dx.doi.org/10.1002/1878-0261.13285 Text en © 2022 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Reviews
Clarke, Thomas L.
Mostoslavsky, Raul
DNA repair as a shared hallmark in cancer and ageing
title DNA repair as a shared hallmark in cancer and ageing
title_full DNA repair as a shared hallmark in cancer and ageing
title_fullStr DNA repair as a shared hallmark in cancer and ageing
title_full_unstemmed DNA repair as a shared hallmark in cancer and ageing
title_short DNA repair as a shared hallmark in cancer and ageing
title_sort dna repair as a shared hallmark in cancer and ageing
topic Reviews
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9490147/
https://www.ncbi.nlm.nih.gov/pubmed/35834102
http://dx.doi.org/10.1002/1878-0261.13285
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