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Evidence shows that epigenetic mutations and misplacement of these marks can promote disease, making epigenetic mechanisms, interactions, and dysregulation key biomedical targets. 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An Update of Epigenetic Drugs for the Treatment of Cancers and Brain Diseases: A Comprehensive Review. Genes 2023, 14, 873. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)genes14040873  \nAcademic Editors: Marzena Ma´ckowiak and Dubravka Švob Štrac  \nReceived: 16 November 2022  \nRevised: 28 December 2022  \nAccepted: 3 April 2023  \nPublished: 6 April 2023  \nCopyright: © 2023 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 ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \nDepartment of Biophysics, Faculty of Biological Sciences, Tarbiat Modares University, Jalal Ale Ahmad Highway, Tehran P.O. Box 14115-111, Iran  \n* Correspondence: [a-allahverdi@modares.ac.ir](a-allahverdi@modares.ac.ir); Tel.: +98-21-8288-4749 † These authors contributed equally to this work.  \nAbstract: Epigenetics has long been recognized as a significant field in biology and is defined asthe investigation of any alteration in gene expression patterns that is not attributed to changes in the DNA sequences. Epigenetic marks, including histone modifications, non-coding RNAs, and DNA methylation, play crucial roles in gene regulation. Numerous studies in humans have been carried out on single-nucleotide resolution of DNA methylation, the CpG island, new histone modifications, and genome-wide nucleosome positioning. These studies indicate that epigenetic mutations and aberrant placement of these epigenetic marks play a critical role in causing the disease. Consequently, significant development has occurred in biomedical research in identifying epigenetic mechanisms, their interactions, and changes in health and disease conditions. The purpose of this review article is to provide comprehensive information about the different types of diseases caused by alterations in epigenetic factors such as DNA methylation and histone acetylation or methylation. Recent studies reported that epigenetics could influence the evolution of human cancer via aberrant methylation of gene promoter regions, which is associated with reduced gene function. Furthermore, DNA methyltransferases (DNMTs) in the DNA methylation process as well as histone acetyltransferases (HATs)/histone deacetylases (HDACs) and histone methyltransferases (HMTs)/demethylases (HDMs) in histone modifications play important roles both in the catalysis and inhibition of target gene transcription and in many other DNA processes such as repair, replication, and recombination. Dysfunction in these enzymes leads to epigenetic disorders and, as a result, various diseases such as cancers and brain diseases. Consequently, the knowledge of how to modify aberrant DNA methylation as well as aberrant histone acetylation or methylation via inhibitors by using epigenetic drugs can be a suitable therapeutic approach for a number of diseases. Using the synergistic effects of DNA methylation and histone modification inhibitors, it is hoped that many epigenetic defects will be treated in the future. Numerous studies have demonstrated a link between epigenetic marks and their effects on brain and cancer diseases. Designing appropriate drugs could provide novel strategies for the management of these diseases in the near future.  \nKeywords: epigenetic disorders; epigenetic therapy; DNA methylation; DNA methyltransferases; histone modifications; personalized medicine  \n1. Introduction  \n1.1. Epigenetics Overview  \n“Epigenetics” was initially described by British developmental scholar Conrad Waddington in the 1940s as “a new field of research in biology","cbCaiaTkDrsbTkUs","https://ap.wps.com/l/cbCaiaTkDrsbTkUs","pdf",2279211,34,"English","# Abstract\n# 1. Introduction\n## 1.1. Epigenetics Overview\n## 1.2. Non-Coding RNAs","[{\"question\":\"What is epigenetics and how does it affect gene expression?\",\"answer\":\"Epigenetics refers to changes in gene expression patterns that are not due to DNA sequence alterations. It is driven by epigenetic marks such as histone modifications, non-coding RNAs, and DNA methylation.\"},{\"question\":\"Which epigenetic mechanisms are highlighted as important in disease development?\",\"answer\":\"The review emphasizes how aberrant placement or mutations of epigenetic marks can contribute to disease. It particularly discusses disruptions related to DNA methylation and histone acetylation or methylation.\"},{\"question\":\"How do epigenetic drugs potentially support cancer and brain disease treatment?\",\"answer\":\"By using inhibitors that target enzymes involved in DNA methylation and histone modifications, epigenetic drugs may correct aberrant epigenetic states. The review also notes that synergistic effects of such inhibitors may improve future therapeutic outcomes.\"}]","An Update of Epigenetic Drugs for the Treatment of Cancers and Brain Diseases - A Comprehensive Review | PDF",1790227124,86]