Epigenetic Regulators of DNA Cytosine Modification: Promising Targets for Cancer Therapy
Epigenetic modifications are crucial regulators of gene expression that critically impact cell lineage differentiation, survival, and proliferation, and dysregulations are commonly observed in various cancers. The aberrantly modified epigenome confers unique features on tumor cells, including sustai...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/3/654 |
| _version_ | 1797613375773999104 |
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| author | Inkyung Jung Jungeun An Myunggon Ko |
| author_facet | Inkyung Jung Jungeun An Myunggon Ko |
| author_sort | Inkyung Jung |
| collection | DOAJ |
| description | Epigenetic modifications are crucial regulators of gene expression that critically impact cell lineage differentiation, survival, and proliferation, and dysregulations are commonly observed in various cancers. The aberrantly modified epigenome confers unique features on tumor cells, including sustained proliferative potential, resistance to growth-suppressive or cell death signals, augmented replicative immortality, invasion, and metastasis. As a result, epigenetic abnormalities exhibit significant impacts on all stages of oncogenesis from its onset to progression to metastasis. Among various epigenetic mechanisms in mammals, DNA cytosine methylation–demethylation is recurrently disrupted in cancers. Due to its inherent reversibility, targeting DNA methylation dynamics has gained tremendous attention as a promising therapeutic option that can ameliorate the effects of cancer-specific epigenetic abnormalities by restoring normal conditions. Various small molecules targeting DNA (de)methylation regulators have been developed as potential cancer therapeutics, some of which are approved for usage in clinics. Clinical trials of many other molecules are underway for both hematological malignancies and solid tumors. In this review, we discuss the DNA methylation/demethylation pathway as a promising target for therapeutic intervention in cancer and highlight the development of various epigenetic drugs targeting DNA-modifying enzymes such as DNA methyltransferases (DNMTs) and ten-eleven translocation (TET) enzymes. |
| first_indexed | 2024-03-11T06:54:57Z |
| format | Article |
| id | doaj.art-dc5a314507c8470a9b39a80fa354c28c |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-11T06:54:57Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
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| series | Biomedicines |
| spelling | doaj.art-dc5a314507c8470a9b39a80fa354c28c2023-11-17T09:43:39ZengMDPI AGBiomedicines2227-90592023-02-0111365410.3390/biomedicines11030654Epigenetic Regulators of DNA Cytosine Modification: Promising Targets for Cancer TherapyInkyung Jung0Jungeun An1Myunggon Ko2Department of Biological Sciences, Ulsan National Institute of Science and Technology, Ulsan 44919, Republic of KoreaDepartment of Life Sciences, Jeonbuk National University, Jeonju 54896, Republic of KoreaDepartment of Biological Sciences, Ulsan National Institute of Science and Technology, Ulsan 44919, Republic of KoreaEpigenetic modifications are crucial regulators of gene expression that critically impact cell lineage differentiation, survival, and proliferation, and dysregulations are commonly observed in various cancers. The aberrantly modified epigenome confers unique features on tumor cells, including sustained proliferative potential, resistance to growth-suppressive or cell death signals, augmented replicative immortality, invasion, and metastasis. As a result, epigenetic abnormalities exhibit significant impacts on all stages of oncogenesis from its onset to progression to metastasis. Among various epigenetic mechanisms in mammals, DNA cytosine methylation–demethylation is recurrently disrupted in cancers. Due to its inherent reversibility, targeting DNA methylation dynamics has gained tremendous attention as a promising therapeutic option that can ameliorate the effects of cancer-specific epigenetic abnormalities by restoring normal conditions. Various small molecules targeting DNA (de)methylation regulators have been developed as potential cancer therapeutics, some of which are approved for usage in clinics. Clinical trials of many other molecules are underway for both hematological malignancies and solid tumors. In this review, we discuss the DNA methylation/demethylation pathway as a promising target for therapeutic intervention in cancer and highlight the development of various epigenetic drugs targeting DNA-modifying enzymes such as DNA methyltransferases (DNMTs) and ten-eleven translocation (TET) enzymes.https://www.mdpi.com/2227-9059/11/3/654epigeneticsDNMTTET dioxygenasesDNA methylation and demethylationsmall moleculescancer therapy |
| spellingShingle | Inkyung Jung Jungeun An Myunggon Ko Epigenetic Regulators of DNA Cytosine Modification: Promising Targets for Cancer Therapy Biomedicines epigenetics DNMT TET dioxygenases DNA methylation and demethylation small molecules cancer therapy |
| title | Epigenetic Regulators of DNA Cytosine Modification: Promising Targets for Cancer Therapy |
| title_full | Epigenetic Regulators of DNA Cytosine Modification: Promising Targets for Cancer Therapy |
| title_fullStr | Epigenetic Regulators of DNA Cytosine Modification: Promising Targets for Cancer Therapy |
| title_full_unstemmed | Epigenetic Regulators of DNA Cytosine Modification: Promising Targets for Cancer Therapy |
| title_short | Epigenetic Regulators of DNA Cytosine Modification: Promising Targets for Cancer Therapy |
| title_sort | epigenetic regulators of dna cytosine modification promising targets for cancer therapy |
| topic | epigenetics DNMT TET dioxygenases DNA methylation and demethylation small molecules cancer therapy |
| url | https://www.mdpi.com/2227-9059/11/3/654 |
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