Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Cervena, Klara, Siskova, Anna, Buchler, Tomas, Vodicka, Pavel, Vymetalkova, Veronika
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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
_version_ 1783557036053626880
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
work_keys_str_mv AT cervenaklara methylationbasedtherapiesforcolorectalcancer
AT siskovaanna methylationbasedtherapiesforcolorectalcancer
AT buchlertomas methylationbasedtherapiesforcolorectalcancer
AT vodickapavel methylationbasedtherapiesforcolorectalcancer
AT vymetalkovaveronika methylationbasedtherapiesforcolorectalcancer