Methylation-Based Therapies for Colorectal Cancer
1
Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Videnska 1083, 14 200 Prague, Czech Republic
2
Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Albertov 4, 128 00 Prague, Czech Republic
3
Department of Oncology, First Faculty of Medicine, Charles University and Thomayer Hospital, Videnska 800, 140 59 Prague, Czech Republic
4
Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 76, 323 00 Pilsen, Czech Republic
*
Author to whom correspondence should be addressed.
Cells 2020, 9(6), 1540; https://doi.org/10.3390/cells9061540
Received: 1 June 2020
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Revised: 22 June 2020
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Accepted: 23 June 2020
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Published: 24 June 2020
(This article belongs to the Special Issue DNA Methylation and Its Application in Cancer Therapy)
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.
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Keywords:
colorectal cancer; methylation; DNMT inhibitors; therapy
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MDPI and ACS Style
Cervena, K.; Siskova, A.; Buchler, T.; Vodicka, P.; Vymetalkova, V. Methylation-Based Therapies for Colorectal Cancer. Cells 2020, 9, 1540. https://doi.org/10.3390/cells9061540
AMA Style
Cervena K, Siskova A, Buchler T, Vodicka P, Vymetalkova V. Methylation-Based Therapies for Colorectal Cancer. Cells. 2020; 9(6):1540. https://doi.org/10.3390/cells9061540
Chicago/Turabian StyleCervena, Klara, Anna Siskova, Tomas Buchler, Pavel Vodicka, and Veronika Vymetalkova. 2020. "Methylation-Based Therapies for Colorectal Cancer" Cells 9, no. 6: 1540. https://doi.org/10.3390/cells9061540
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