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      The pharmacoepigenetic paradigm in cancer treatment

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          Abstract

          Epigenetic modifications, characterized by changes in gene expression without altering the DNA sequence, play a crucial role in the development and progression of cancer by significantly influencing gene activity and cellular function. This insight has led to the development of a novel class of therapeutic agents, known as epigenetic drugs. These drugs, including histone deacetylase inhibitors, histone acetyltransferase inhibitors, histone methyltransferase inhibitors, and DNA methyltransferase inhibitors, aim to modulate gene expression to curb cancer growth by uniquely altering the epigenetic landscape of cancer cells. Ongoing research and clinical trials are rigorously evaluating the efficacy of these drugs, particularly their ability to improve therapeutic outcomes when used in combination with other treatments. Such combination therapies may more effectively target cancer and potentially overcome the challenge of drug resistance, a significant hurdle in cancer therapy. Additionally, the importance of nutrition, inflammation control, and circadian rhythm regulation in modulating drug responses has been increasingly recognized, highlighting their role as critical modifiers of the epigenetic landscape and thereby influencing the effectiveness of pharmacological interventions and patient outcomes. Epigenetic drugs represent a paradigm shift in cancer treatment, offering targeted therapies that promise a more precise approach to treating a wide spectrum of tumors, potentially with fewer side effects compared to traditional chemotherapy. This progress marks a step towards more personalized and precise interventions, leveraging the unique epigenetic profiles of individual tumors to optimize treatment strategies.

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          Chromatin modifications and their function.

          The surface of nucleosomes is studded with a multiplicity of modifications. At least eight different classes have been characterized to date and many different sites have been identified for each class. Operationally, modifications function either by disrupting chromatin contacts or by affecting the recruitment of nonhistone proteins to chromatin. Their presence on histones can dictate the higher-order chromatin structure in which DNA is packaged and can orchestrate the ordered recruitment of enzyme complexes to manipulate DNA. In this way, histone modifications have the potential to influence many fundamental biological processes, some of which may be epigenetically inherited.
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            Non-coding RNAs in human disease.

            The relevance of the non-coding genome to human disease has mainly been studied in the context of the widespread disruption of microRNA (miRNA) expression and function that is seen in human cancer. However, we are only beginning to understand the nature and extent of the involvement of non-coding RNAs (ncRNAs) in disease. Other ncRNAs, such as PIWI-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), transcribed ultraconserved regions (T-UCRs) and large intergenic non-coding RNAs (lincRNAs) are emerging as key elements of cellular homeostasis. Along with microRNAs, dysregulation of these ncRNAs is being found to have relevance not only to tumorigenesis, but also to neurological, cardiovascular, developmental and other diseases. There is great interest in therapeutic strategies to counteract these perturbations of ncRNAs.
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              Toll-like Receptors and the Control of Immunity

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                Author and article information

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                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                24 April 2024
                2024
                : 15
                : 1381168
                Affiliations
                [1] 1 Cancer Research Group (CRG) , Faculty of Medicine , Universidad de Las Américas , Quito, Ecuador
                [2] 2 Facultad de Ingenierías y Ciencias Aplicadas , Universidad Internacional SEK , Quito, Ecuador
                [3] 3 German Cancer Research Center (DKFZ) , Faculty of Biosciences , Heidelberg University , Heidelberg, Germany
                [4] 4 Centro de Referencia Nacional de Genómica , Secuenciación y Bioinformática , Instituto Nacional de Investigación en Salud Pública “Leopoldo Izquieta Pérez” , Quito, Ecuador
                [5] 5 Latin American Network for the Implementation and Validation of Clinical Pharmacogenomics Guidelines (RELIVAF-CYTED) , Santiago, Chile
                [6] 6 Deutsche Gesellschaft für Internationale Zusammenarbeit Gmbh , Quito, Ecuador
                Author notes

                Edited by: Elixabet Lopez-Lopez, University of the Basque Country, Spain

                Reviewed by: Marcella Barbarino, University of Siena, Italy

                Tamas Gonda, New York University, United States

                *Correspondence: Andrés López-Cortés, aalc84@ 123456gmail.com
                Article
                1381168
                10.3389/fphar.2024.1381168
                11076712
                38720770
                f0d2e389-9eb7-4f6c-8acc-67b4c1127161
                Copyright © 2024 Ocaña-Paredes, Rivera-Orellana, Ramírez-Sánchez, Montalvo-Guerrero, Freire, Espinoza-Ferrao, Altamirano-Colina, Echeverría-Espinoza, Ramos-Medina, Echeverría-Garcés, Granda-Moncayo, Jácome-Alvarado, Andrade and López-Cortés.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 02 February 2024
                : 11 April 2024
                Funding
                The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Latin American Society of Pharmacogenomics and Personalized Medicine (SOLFAGEM). Publication of this article was funded by Universidad de Las Américas from Quito, Ecuador.
                Categories
                Pharmacology
                Review
                Custom metadata
                Pharmacogenetics and Pharmacogenomics

                Pharmacology & Pharmaceutical medicine
                epigenetic drugs,histone deacetylase inhibitors,histone acetyltransferase inhibitors,histone methyltransferase inhibitors,dna methyltransferase inhibitors,clinical trials

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