2019
DOI: 10.1186/s13148-019-0776-0
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The timeline of epigenetic drug discovery: from reality to dreams

Abstract: The flexibility of the epigenome has generated an enticing argument to explore its reversion through pharmacological treatments as a strategy to ameliorate disease phenotypes. All three families of epigenetic proteins—readers, writers, and erasers—are druggable targets that can be addressed through small-molecule inhibitors. At present, a few drugs targeting epigenetic enzymes as well as analogues of epigenetic modifications have been introduced into the clinic use (e.g. to treat haematological malignancies), … Show more

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Cited by 294 publications
(265 citation statements)
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“… 169 Nevertheless, adverse reactions to epidrugs may emerge due to their pleiotropic effects on gene expression, their activity on non-histone targets, or their interaction with non-tumoural cells. 31 , 170 The specificity issues of epigenetic drugs are difficult to harness, as the diversity of their biological effects depends not only on the quality of their chemical design, but mostly on the complex functional interactions among their targets, as previously discussed. Accumulating evidence indicates that epidrug toxicity may be averted or attenuated by modifying the administration strategies.…”
Section: Resultsmentioning
confidence: 99%
“… 169 Nevertheless, adverse reactions to epidrugs may emerge due to their pleiotropic effects on gene expression, their activity on non-histone targets, or their interaction with non-tumoural cells. 31 , 170 The specificity issues of epigenetic drugs are difficult to harness, as the diversity of their biological effects depends not only on the quality of their chemical design, but mostly on the complex functional interactions among their targets, as previously discussed. Accumulating evidence indicates that epidrug toxicity may be averted or attenuated by modifying the administration strategies.…”
Section: Resultsmentioning
confidence: 99%
“…Thus, a new epigenetic field is currently emerging, i.e., pharmacoepigenomics, which aims to develop and test drugs specifically targeting epigenetic alterations related to cancer [128]. The drugs developed so far are inhibitors of DNA-methyltransferases (DNMTs), histone methyltransferases (HMTs), demethylases (HDMs) or deacetylases (HDACs); these drugs act upon crucial molecules for epigenetic modifications, as previously described ( Figure 5) [128,129]. These drugs [11] are potentially useful to reverse the epigenetic status of gene promoters, or in their associated histones.…”
Section: Therapies Targeting Methylation In Hox-associated Cancersmentioning
confidence: 99%
“…37 These epigenetic drugs are able to reexpress silenced genes, either by demethylation of methylated promoter regions (demethylating agents) or by histone acetylation. 38 Several compounds have been preclinically tested and showed promising results in other cancers and HCC as 5-azacytidine (Vidaza), 5-aza-dC (decitabine), MS-275, and Valproic Acid. 39 Therefore, we recommend performing quantitative analysis of methylated gene p16 in large cohorts with liver cirrhosis especially for high-risk patients who had suggestive clinical manifestations of HCC as loss of weight, repeatedly hepatic encephalopathy without evidence of predisposing factors or rapid accumulating ascites even without focal lesion(s) in imaging.…”
Section: Discussionmentioning
confidence: 99%