کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8920228 | 1643347 | 2017 | 22 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Epigenetics: Druggable targets for anti-cancer therapies
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
Epigenetic alterations of a cell are manifested through various mechanisms including DNA methylation, histone modification, nucleosome remodeling and other non-coding mediated pathways. An abnormal expression pattern or genomic alterations in above-mentioned epigenetic regulators can lead to the induction and maintenance of various cancers. Several protein complexes which are known to manipulate these epigenetic regulators alterations, consequently contribute in carcinogenic processes. Therefore, several protein complexes associated DNA methylation and histone modification became druggable targets for cancer treatment. A few epigenetic agents have been approved for cancer treatment. Toxicological profiles of these approved epigenetic agents include hematological and gastrointestinal effects and/or alteration of cardiac electrical properties leading to the prolongation of QTc interval (a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle, corrected for heart rate). Also, these epigenetic agents pose potential risk to fertility and embryofetal development in humans, likely due to their pharmacologic activity and/or antiproliferative effects. Additional safety concerns related to therapeutic manipulation of epigenetic regulation include reports of viral reactivation in humans and potential deleterious effects on germ cell homeostasis and possible inherited, transgenerational effects. This article presents a simple overview of various covalent modifications of DNA and histone, druggability of these modifications in the context of cancer treatment, known safety profiles of epigenetic drugs approved for cancer treatment and potential risks associated with therapeutic manipulation of epigenetic regulation.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Current Opinion in Toxicology - Volume 6, October 2017, Pages 79-86
Journal: Current Opinion in Toxicology - Volume 6, October 2017, Pages 79-86
نویسندگان
Kaushik Datta, Kyle Kolaja,