DNA Repair Pathway Alterations in Bladder Cancer

Most bladder tumors have complex genomes characterized by a high mutation burden as well as frequent copy number alterations and chromosomal rearrangements. Alterations in DNA repair pathways—including the double-strand break (DSB) and nucleotide excision repair (NER) pathways—are present in bladder...

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Main Author: Kent W. Mouw
Format: Article
Language:English
Published: MDPI AG 2017-03-01
Series:Cancers
Subjects:
Online Access:http://www.mdpi.com/2072-6694/9/4/28
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author Kent W. Mouw
author_facet Kent W. Mouw
author_sort Kent W. Mouw
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description Most bladder tumors have complex genomes characterized by a high mutation burden as well as frequent copy number alterations and chromosomal rearrangements. Alterations in DNA repair pathways—including the double-strand break (DSB) and nucleotide excision repair (NER) pathways—are present in bladder tumors and may contribute to genomic instability and drive the tumor phenotype. DNA damaging such as cisplatin, mitomycin C, and radiation are commonly used in the treatment of muscle-invasive or metastatic bladder cancer, and several recent studies have linked specific DNA repair pathway defects with sensitivity to DNA damaging-based therapy. In addition, tumor DNA repair defects have important implications for use of immunotherapy and other targeted agents in bladder cancer. Therefore, efforts to further understand the landscape of DNA repair alterations in bladder cancer will be critical in advancing treatment for bladder cancer. This review summarizes the current understanding of the role of DNA repair pathway alterations in bladder tumor biology and response to therapy.
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spelling doaj.art-4d8bf91ea3854da382582d5c4c82ad6b2023-09-03T02:00:00ZengMDPI AGCancers2072-66942017-03-01942810.3390/cancers9040028cancers9040028DNA Repair Pathway Alterations in Bladder CancerKent W. Mouw0Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham & Women’s Hospital, Harvard Medical School, Boston, MA 02215, USAMost bladder tumors have complex genomes characterized by a high mutation burden as well as frequent copy number alterations and chromosomal rearrangements. Alterations in DNA repair pathways—including the double-strand break (DSB) and nucleotide excision repair (NER) pathways—are present in bladder tumors and may contribute to genomic instability and drive the tumor phenotype. DNA damaging such as cisplatin, mitomycin C, and radiation are commonly used in the treatment of muscle-invasive or metastatic bladder cancer, and several recent studies have linked specific DNA repair pathway defects with sensitivity to DNA damaging-based therapy. In addition, tumor DNA repair defects have important implications for use of immunotherapy and other targeted agents in bladder cancer. Therefore, efforts to further understand the landscape of DNA repair alterations in bladder cancer will be critical in advancing treatment for bladder cancer. This review summarizes the current understanding of the role of DNA repair pathway alterations in bladder tumor biology and response to therapy.http://www.mdpi.com/2072-6694/9/4/28urothelial cancerbladder cancerDNA repairnucleotide excision repairmutational signaturegenomic instability
spellingShingle Kent W. Mouw
DNA Repair Pathway Alterations in Bladder Cancer
Cancers
urothelial cancer
bladder cancer
DNA repair
nucleotide excision repair
mutational signature
genomic instability
title DNA Repair Pathway Alterations in Bladder Cancer
title_full DNA Repair Pathway Alterations in Bladder Cancer
title_fullStr DNA Repair Pathway Alterations in Bladder Cancer
title_full_unstemmed DNA Repair Pathway Alterations in Bladder Cancer
title_short DNA Repair Pathway Alterations in Bladder Cancer
title_sort dna repair pathway alterations in bladder cancer
topic urothelial cancer
bladder cancer
DNA repair
nucleotide excision repair
mutational signature
genomic instability
url http://www.mdpi.com/2072-6694/9/4/28
work_keys_str_mv AT kentwmouw dnarepairpathwayalterationsinbladdercancer