Clinical Applications of Histone Deacetylase Inhibitors

Park, Jeenah; Terranova-Barberio, Manuela; Zhong, Allison Y.; Thomas, Scott; Münster, Pamela N.

doi:10.1016/b978-0-12-805388-1.00040-7

Cited by 8 publications

(9 citation statements)

References 141 publications

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“…Notably, entinostat has generally been well tolerated in clinical trials, with most side effects being mild to moderate and manageable with supportive care [ 48 ]. The differential inhibition between wild-type and CDH1 -null cells was frequently statistically significant at sub-micromolar concentrations and consistent with the effective concentrations observed in numerous cancer cell lines [ 17 , 48 , 49 ].…”

Section: Discussionsupporting

confidence: 79%

“…HDAC inhibitors exert their anticancer effects through a range of cytotoxic or cytostatic mechanisms that are likely to be context dependent, including cell-cycle arrest, apoptosis and promotion of a terminally differentiated state [ 17 , 42 ]. We observed strong pro-apoptotic effects for each of entinostat, pracinostat, mocetinostat and vorinostat in the NCI-N87 cell lines.…”

Section: Discussionmentioning

confidence: 99%

“…Histone deacetylases are proteins involved in post-translational modification of diverse histone and non-histone proteins through the removal of acetyl groups from the ε-amino group of lysine [ 16 , 17 ]. HDACs are implicated in diverse biological processes, including tissue developmental programming and apoptosis, and have a well-established role in transcriptional control [ 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

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E-Cadherin-Deficient Epithelial Cells Are Sensitive to HDAC Inhibitors

Decourtye-Espiard

Bougen-Zhukov

Godwin

et al. 2021

Cancers

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Inactivating germline mutations in the CDH1 gene (encoding the E-cadherin protein) are the genetic hallmark of hereditary diffuse gastric cancer (HDGC), and somatic CDH1 mutations are an early event in the development of sporadic diffuse gastric cancer (DGC) and lobular breast cancer (LBC). In this study, histone deacetylase (HDAC) inhibitors were tested for their ability to preferentially inhibit the growth of human cell lines (MCF10A and NCI-N87) and murine organoids lacking CDH1 expression. CDH1−/− breast and gastric cells were more sensitive to the pan-HDAC inhibitors entinostat, pracinostat, mocetinostat and vorinostat than wild-type cells, with an elevated growth inhibition that was, in part, attributable to increased apoptosis. CDH1-null cells were also sensitive to more class-specific HDAC inhibitors, but compared to the pan-inhibitors, these effects were less robust to genetic background. Increased sensitivity to entinostat was also observed in gastric organoids with both Cdh1 and Tp53 deletions. However, the deletion of Tp53 largely abrogated the sensitivity of the Cdh1-null organoids to pracinostat and mocetinostat. Finally, entinostat enhanced Cdh1 expression in heterozygous Cdh1+/− murine organoids. In conclusion, entinostat is a promising drug for the chemoprevention and/or treatment of HDGC and may also be beneficial for the treatment of sporadic CDH1-deficient cancers.

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Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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E-Cadherin-Deficient Epithelial Cells Are Sensitive to HDAC Inhibitors

Decourtye-Espiard

Bougen-Zhukov

Godwin

et al. 2021

Cancers

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“…However, it is to be noted that most of them inhibit HDACs I and/or II, both of which are class I HDACs. 92 One study 91 evaluated the use of the naturally occurring compound lactate which was found to promote resilience to stress in mice by modulating the activity of HDACs. Table 4 lists the clinical trials of epigenetic drugs in the treatment of anxiety.…”

Section: Rat Hippocampusmentioning

confidence: 99%

“…Clinically useful HDACi are classified according to their chemical structure 92 into hydroxamic acids (vorinostat or SAHA, panobinostat, belinostat, TSA, quisinostat, rocilinostat, and abexinostat), short chain fatty acids (butyrate and valproic acid), cyclic peptides (romidepsin), and benzamides (mocetinostat or MGCD0103 and entinostat or MS-275). Most currently available HDACi inhibit classes I, II, and IV of the HDACs, but not SIRT enzymes.…”

Section: Implications Of Trials Of Epigenetic Drugs In Anxiety Disordersmentioning

confidence: 99%

<p>The Potential Role of Epigenetic Drugs in the Treatment of Anxiety Disorders</p>

Peedicayil¹

2020

NDT

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There is increasing evidence that abnormalities in epigenetic mechanisms of gene expression contribute to the pathogenesis of anxiety disorders (ADs). This article discusses the role of epigenetic mechanisms of gene expression in the pathogenesis of ADs. It also discusses the data so far obtained from preclinical and clinical trials on the use of epigenetic drugs for treating ADs. Most drug trials investigating the use of epigenetic drugs for treating ADs have used histone deacetylase inhibitors (HDACi). HDACi are showing favorable results in both preclinical and clinical drug trials for treating ADs. However, at present the mode of action of HDACi in ADs is not clear. More work needs to be done to elucidate how epigenetic dysregulation contributes to the pathogenesis of ADs. More work also needs to be done on the mode of action of HDACi in alleviating the signs and symptoms of ADs.

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Recent histone deacetylase inhibitors in cancer therapy

Parveen,

Harihar,

Chatterji

2023

Cancer

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Cancer metastasis increases the complexity of the disease and escalates patient mortality. Traditional chemotherapy has been associated with low efficacy and marked side effects. Studies pivot toward histone deacetylase (HDAC) enzymes and inhibitors because they are critical for chromatin structure, gene regulation, and cellular activities that are linked to metastasis and cancer progression. HDAC inhibitors (HDACi) can alter gene expression patterns and can lead to cell‐cycle arrest and apoptosis in neoplastic cells. Several HDACi drugs like vorinostat, romidepsin, panobinostat, and belinostat are approved by the Food and Drug Administration. China and Japan have approved the use of tucidinostat, a new subtype‐selective HDACi that inhibits class 1 HDAC1, HDAC2, HDAC3, as well as class 2b HDAC10. These drugs have shown promising results in the treatment of multiple carcinoma including cervical cancer, T‐cell lymphoma, brain cancer, and breast cancer. This review highlights the HDACi classes, the mechanism of action of these inhibitors, their preclinical and clinical efficacy, and the latest clinical trials and patents used in cancer therapeutics. Overall, this review focuses on patents and clinical trials data from 2019 onward to give a better viewpoint on current trends in HDACis as chemotherapy agents.

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Clinical Applications of Histone Deacetylase Inhibitors

Cited by 8 publications

References 141 publications

E-Cadherin-Deficient Epithelial Cells Are Sensitive to HDAC Inhibitors

E-Cadherin-Deficient Epithelial Cells Are Sensitive to HDAC Inhibitors

<p>The Potential Role of Epigenetic Drugs in the Treatment of Anxiety Disorders</p>

Recent histone deacetylase inhibitors in cancer therapy

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