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Wednesday, July 26, 2017 9:18:24 AM
I was unaware of the category.
And I am certainly unqualified to even guess at any potential
positive or negative effect of combining DCVAX with this category
of drugs.
With that out of the way .....
WOW - THANKS for finding this class of drugs .....
OVERVIEW
Use of Epigenetic Drugs in Disease: An Overview
Epigenetic changes such as DNA methylation and histone methylation and acetylation alter gene expression at the level of transcription by upregulating, downregulating, or silencing genes completely.
In this review, we discuss the major classes of epigenetic drugs currently in use, such as DNA methylation inhibiting drugs, bromodomain inhibitors, histone acetyl transferase inhibitors, histone deacetylase inhibitors, protein methyltransferase inhibitors, and histone methylation inhibitors and their role in reversing epigenetic changes and treating disease.
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HEDD: the human epigenetic drug database
In the past decades, epigenetics has emerged as a novel and important research area in drug discovery, which includes most of the human pathology in which deregulation in gene expression is observed (8). Historically, compounds that demonstrated DNA methyltransferase inhibitor (DNMTi) activity in cells were cytidine analogs decitabine and azacitidine; and these were approved for myelodysplastic syndrome (MDS) treatment (9). Moreover, hydralazine and procainamide have been approved for hypertension and cardiac arrhythmia treatment, respectively. Recently, its activity as DNMTi has been discovered (10). The histone deacetylase inhibitor (HDACi) vorinostat and romidepsin were approved by the FDA (Food and Drug Administration) for cutaneous T-cell lymphoma (CTCL) (8, 11). Panobinostat and belinostat are FDA approved for the treatment of multiple myeloma (MM) and peripheral T-cell lymphoma (PTCL), respectively (12, 13). These compounds are clear examples of the therapeutic relevance of ‘first generation’ of epigenetic drugs for clinical application, which are DNMTis and HDACis
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The future of epigenetic drugs
Epigenetic drugs are incredibly potent and can help reverse abnormal gene expression that can result in various diseases.
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TRIALS - 2012
Trials with ‘epigenetic’ drugs: An update
www.sciencedirect.com/science/article/pii/S1574789112000968
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GBM
The good, the bad and the ugly: Epigenetic mechanisms in glioblastoma
Third, genetic disruptions directly within the core epigenetic machinery, exemplified by the recently identified mutations within isocitrate dehydrogenase genes IDH1/2 and variant histone genes H3.3/H3F3A. These constitute the ‘good, the bad and the ugly’ of epigenetic mechanisms in cancer.
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Advances in epigenetic glioblastoma therapy
Over the last decade, numerous preclinical and clinical studies on histone deacetylase (HDAC) inhibitors have shown promising results in various cancers. This article provides an overview of the anticancer mechanisms of HDAC inhibitors and the role of HDAC isoforms in GBM. We also summarize current knowledge on HDAC inhibitors on the basis of preclinical studies and emerging clinical data.
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SURVIVAL
Epigenetics Drug Improves Survival in the Second Deadliest Cancer
New results from 4SC indicate that its epigenetics drug resminostat can make a big difference in the survival of liver cancer patients with poor prognosis.
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REPOSITIONING FDA-APPROVED DRUGS IN COMBINATION WITH EPIGENETIC DRUGS TO REPROGRAM COLON CANCER EPIGENOME
Epigenetic drugs, such as DNA methylation inhibitors (DNMTi) or histone deacetylase inhibitors (HDACi), are approved in monotherapy for cancer treatment. These drugs reprogram gene expression profiles, reactivate tumor suppressor genes (TSG) producing cancer cell differentiation and apoptosis. Epigenetic drugs have been shown to synergize with other epigenetic drugs or various anticancer drugs.
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GBM Trial - 1 example
Vorinostat and Bortezomib in Treating Patients With Progressive, Recurrent Glioblastoma Multiforme
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Vorinostat With or Without Isotretinoin in Treating Young Patients With Recurrent or Refractory Solid Tumors, Lymphoma, or Leukemia
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BAD EFFECT
Combined Treatment of ATRA with Epigenetic Drugs Increases Aggressiveness of Glioma Xenografts.
CONCLUSION:
Combining ATRA with epigenetic drug therapies led to the unwanted opposite effect and increased aggressiveness of glioma xenografts, arguing against future clinical applications of such combinations
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