Special Issue "Epigenetic Cancer Therapy: Targeting DNA and Histone Methylation"
A special issue of Epigenomes (ISSN 2075-4655).
Deadline for manuscript submissions: closed (1 May 2021).
Interests: epigenetic therapy cancer; inhibitors DNA methylation; inhibitors of EZH2
Epigenetic silencing of genes that suppress malignancy by DNA and histone methylation plays an important role in the development of cancer. Several observations suggest that these epigenetic alterations are promising targets for chemotherapeutic intervention. The potent inhibitor of DNA methylation, 5-Aza-2’-deoxycytidine (5AZA-CdR, decitabine), was shown to induce remissions in patients with acute myeloid leukemia (AML). However, these remissions were of limited duration, possibly due to suboptimal activation of tumor suppressor genes (TSGs) by 5AZA-CdR due to the presence of a second gene-silencing marker, such as histone H3-trimethylated lysine 27 (H3K27me3). EZH2 catalyzes the methylation of H3K27, and 3-deazaneplanocin-A (DZNep), a potent inhibitor of EZH2, displays potent antineoplastic action against AML cells. The combination of DZNep and 5AZA-CdR exhibits a remarkable antileukemic synergy. Investigations on isocitrate dehydrogenase mutations (mut-IDH) provide additional support that these epigenetic alterations are interesting targets for chemotherapy. AML cells with mut-IDH produce 2-hydroxy-glutarate (2HG), an oncometabolite that inhibits the catalytic activity of the TET family and Jumonji-C histone demethylases (JHDMs). This action blocks the demethylation of DNA and H3K27me3, which prevents TSG reactivation. An intriguing hypothesis to explain these interactions is that cells possess enzymatic mechanisms that attenuate their capacity for excessive proliferation, decreasing the probability of progression to malignancy. This natural enzymatic mechanism has the potential to enhance the effectiveness of 5AZA-CdR and DZNep. This novel epigenetic therapy merits clinical investigation in cancer patients with high priority.
Prof. Richard L. Momparler
Manuscript Submission Information
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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Epigenomes is an international peer-reviewed open access quarterly journal published by MDPI.
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- cancer stem cells
- combination chemotherapy
- histone demethylases
- natural anticancer mechanism