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Alterations of DNA damage repair in cancer: from mechanisms to applications

DNA damage repair (DDR) pathways are essential to ensure the accurate transmission of genetic material. However, different endogenous and exogenous factors challenge genomic integrity. Mechanisms involved in the alterations of DDR pathways mainly include genetic inactivation and epigenetic mechanism...

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Autores principales: Jiang, Minlin, Jia, Keyi, Wang, Lei, Li, Wei, Chen, Bin, Liu, Yu, Wang, Hao, Zhao, Sha, He, Yayi, Zhou, Caicun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812211/
https://www.ncbi.nlm.nih.gov/pubmed/33490197
http://dx.doi.org/10.21037/atm-20-2920
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author Jiang, Minlin
Jia, Keyi
Wang, Lei
Li, Wei
Chen, Bin
Liu, Yu
Wang, Hao
Zhao, Sha
He, Yayi
Zhou, Caicun
author_facet Jiang, Minlin
Jia, Keyi
Wang, Lei
Li, Wei
Chen, Bin
Liu, Yu
Wang, Hao
Zhao, Sha
He, Yayi
Zhou, Caicun
author_sort Jiang, Minlin
collection PubMed
description DNA damage repair (DDR) pathways are essential to ensure the accurate transmission of genetic material. However, different endogenous and exogenous factors challenge genomic integrity. Mechanisms involved in the alterations of DDR pathways mainly include genetic inactivation and epigenetic mechanisms. The development and progression of carcinomas are closely associated with DDR pathway aberrations, including the epigenetic silencing of gene O6-alkylguanine-DNA methyltransferase (MGMT); deficiencies of mismatch repair (MMR) genes, including MutL homolog 1 (MLH1), MutS protein homologue (MSH)-2 (MSH2), MSH6, and PMS1 homolog 2; the mismatch repair system component (PMS2); and mutations of homologous recombination repair (HRR) genes, such as the breast cancer susceptibility gene 1/2 (BRCA1/2). Understanding the underlying mechanisms and the correlations between alterations to DDR pathways and cancer could improve the efficacy of antitumor therapies. Emerging evidence suggests that survival is higher in patients with DDR-deficient tumors than in those with DDR-proficient tumors. Thus, DDR alterations play a predictive and prognostic role in anticancer therapies. Theoretical studies on the co-administration of DDR inhibitors and other anticancer therapies, including chemotherapy, radiotherapy, immunotherapy, endocrine therapy, and epigenetic drugs, hold promise for cancer treatments. In this review, we focus on the basic mechanisms, characteristics, current applications, and combination strategies of DDR pathways in the anticancer field.
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spelling pubmed-78122112021-01-22 Alterations of DNA damage repair in cancer: from mechanisms to applications Jiang, Minlin Jia, Keyi Wang, Lei Li, Wei Chen, Bin Liu, Yu Wang, Hao Zhao, Sha He, Yayi Zhou, Caicun Ann Transl Med Review Article DNA damage repair (DDR) pathways are essential to ensure the accurate transmission of genetic material. However, different endogenous and exogenous factors challenge genomic integrity. Mechanisms involved in the alterations of DDR pathways mainly include genetic inactivation and epigenetic mechanisms. The development and progression of carcinomas are closely associated with DDR pathway aberrations, including the epigenetic silencing of gene O6-alkylguanine-DNA methyltransferase (MGMT); deficiencies of mismatch repair (MMR) genes, including MutL homolog 1 (MLH1), MutS protein homologue (MSH)-2 (MSH2), MSH6, and PMS1 homolog 2; the mismatch repair system component (PMS2); and mutations of homologous recombination repair (HRR) genes, such as the breast cancer susceptibility gene 1/2 (BRCA1/2). Understanding the underlying mechanisms and the correlations between alterations to DDR pathways and cancer could improve the efficacy of antitumor therapies. Emerging evidence suggests that survival is higher in patients with DDR-deficient tumors than in those with DDR-proficient tumors. Thus, DDR alterations play a predictive and prognostic role in anticancer therapies. Theoretical studies on the co-administration of DDR inhibitors and other anticancer therapies, including chemotherapy, radiotherapy, immunotherapy, endocrine therapy, and epigenetic drugs, hold promise for cancer treatments. In this review, we focus on the basic mechanisms, characteristics, current applications, and combination strategies of DDR pathways in the anticancer field. AME Publishing Company 2020-12 /pmc/articles/PMC7812211/ /pubmed/33490197 http://dx.doi.org/10.21037/atm-20-2920 Text en 2020 Annals of Translational Medicine. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Review Article
Jiang, Minlin
Jia, Keyi
Wang, Lei
Li, Wei
Chen, Bin
Liu, Yu
Wang, Hao
Zhao, Sha
He, Yayi
Zhou, Caicun
Alterations of DNA damage repair in cancer: from mechanisms to applications
title Alterations of DNA damage repair in cancer: from mechanisms to applications
title_full Alterations of DNA damage repair in cancer: from mechanisms to applications
title_fullStr Alterations of DNA damage repair in cancer: from mechanisms to applications
title_full_unstemmed Alterations of DNA damage repair in cancer: from mechanisms to applications
title_short Alterations of DNA damage repair in cancer: from mechanisms to applications
title_sort alterations of dna damage repair in cancer: from mechanisms to applications
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812211/
https://www.ncbi.nlm.nih.gov/pubmed/33490197
http://dx.doi.org/10.21037/atm-20-2920
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