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Methylation-Based Therapies for Colorectal Cancer
Colorectal carcinogenesis (CRC) is caused by the gradual long-term accumulation of both genetic and epigenetic changes. Recently, epigenetic alterations have been included in the classification of the CRC molecular subtype, and this points out their prognostic impact. As epigenetic modifications are...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349319/ https://www.ncbi.nlm.nih.gov/pubmed/32599894 http://dx.doi.org/10.3390/cells9061540 |
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author | Cervena, Klara Siskova, Anna Buchler, Tomas Vodicka, Pavel Vymetalkova, Veronika |
author_facet | Cervena, Klara Siskova, Anna Buchler, Tomas Vodicka, Pavel Vymetalkova, Veronika |
author_sort | Cervena, Klara |
collection | PubMed |
description | Colorectal carcinogenesis (CRC) is caused by the gradual long-term accumulation of both genetic and epigenetic changes. Recently, epigenetic alterations have been included in the classification of the CRC molecular subtype, and this points out their prognostic impact. As epigenetic modifications are reversible, they may represent relevant therapeutic targets. DNA methylation, catalyzed by DNA methyltransferases (DNMTs), regulates gene expression. For many years, the deregulation of DNA methylation has been considered to play a substantial part in CRC etiology and evolution. Despite considerable advances in CRC treatment, patient therapy response persists as limited, and their profit from systemic therapies are often hampered by the introduction of chemoresistance. In addition, inter-individual changes in therapy response in CRC patients can arise from their specific (epi)genetic compositions. In this review article, we summarize the options of CRC treatment based on DNA methylation status for their predictive value. This review also includes the therapy outcomes based on the patient’s methylation status in CRC patients. In addition, the current challenge of research is to develop therapeutic inhibitors of DNMT. Based on the essential role of DNA methylation in CRC development, the application of DNMT inhibitors was recently proposed for the treatment of CRC patients, especially in patients with DNA hypermethylation. |
format | Online Article Text |
id | pubmed-7349319 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-73493192020-07-22 Methylation-Based Therapies for Colorectal Cancer Cervena, Klara Siskova, Anna Buchler, Tomas Vodicka, Pavel Vymetalkova, Veronika Cells Review Colorectal carcinogenesis (CRC) is caused by the gradual long-term accumulation of both genetic and epigenetic changes. Recently, epigenetic alterations have been included in the classification of the CRC molecular subtype, and this points out their prognostic impact. As epigenetic modifications are reversible, they may represent relevant therapeutic targets. DNA methylation, catalyzed by DNA methyltransferases (DNMTs), regulates gene expression. For many years, the deregulation of DNA methylation has been considered to play a substantial part in CRC etiology and evolution. Despite considerable advances in CRC treatment, patient therapy response persists as limited, and their profit from systemic therapies are often hampered by the introduction of chemoresistance. In addition, inter-individual changes in therapy response in CRC patients can arise from their specific (epi)genetic compositions. In this review article, we summarize the options of CRC treatment based on DNA methylation status for their predictive value. This review also includes the therapy outcomes based on the patient’s methylation status in CRC patients. In addition, the current challenge of research is to develop therapeutic inhibitors of DNMT. Based on the essential role of DNA methylation in CRC development, the application of DNMT inhibitors was recently proposed for the treatment of CRC patients, especially in patients with DNA hypermethylation. MDPI 2020-06-24 /pmc/articles/PMC7349319/ /pubmed/32599894 http://dx.doi.org/10.3390/cells9061540 Text en © 2020 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 Cervena, Klara Siskova, Anna Buchler, Tomas Vodicka, Pavel Vymetalkova, Veronika Methylation-Based Therapies for Colorectal Cancer |
title | Methylation-Based Therapies for Colorectal Cancer |
title_full | Methylation-Based Therapies for Colorectal Cancer |
title_fullStr | Methylation-Based Therapies for Colorectal Cancer |
title_full_unstemmed | Methylation-Based Therapies for Colorectal Cancer |
title_short | Methylation-Based Therapies for Colorectal Cancer |
title_sort | methylation-based therapies for colorectal cancer |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349319/ https://www.ncbi.nlm.nih.gov/pubmed/32599894 http://dx.doi.org/10.3390/cells9061540 |
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