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An Integrated Platform for Genome-wide Mapping of Chromatin States Using High-throughput ChIP-sequencing in Tumor Tissues
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The pituitary tumour epigenome: aberrations and prospects for targeted therapy

Kiren Yacqub-Usman1, Alan Richardson, Cuong V Duong

  • 1Human Disease and Genomics Group, Institute of Science and Technology in Medicine, School of Medicine, Keele University, Stoke-on-Trent, Staffordshire ST4 7QB, UK.

Nature Reviews. Endocrinology
|April 25, 2012
PubMed

Insights

Epigenetic changes in tumors are reversible. Drugs targeting DNA methyltransferases (DNMTs) and histone deacetylases (HDACs) can restore gene expression and enhance cancer treatments.

Area of Science:

  • Oncology
  • Epigenetics
  • Pharmacology

Background:

  • Epigenetic alterations, including DNA methylation and histone modifications, are characteristic of many tumors, including pituitary tumors.
  • Unlike genetic mutations, epigenetic changes are potentially reversible, offering therapeutic opportunities.

Purpose of the Study:

  • To explore the potential of epigenetic drugs, specifically DNA methyltransferase (DNMT) and histone deacetylase (HDAC) inhibitors, in cancer therapy.
  • To investigate the synergistic effects of combining DNMT and HDAC inhibitors.
  • To assess the efficacy of these drugs in restoring hormone responsiveness and sensitivity to conventional treatments in tumor cells.

Main Methods:

  • Utilized drug treatments targeting DNA methyltransferases (DNMTs) and histone deacetylases (HDACs) in pituitary tumor cell lines.
  • Investigated the combined effects of DNMT and HDAC inhibitors.
  • Assessed drug-induced reversal of transcriptional silencing and its impact on tumor cell apoptosis and receptor status.

Main Results:

  • Drug-induced reversal of epigenetic silencing can restore gene expression, such as the dopamine D(2) receptor.
  • Combination therapy with DNMT and HDAC inhibitors demonstrates enhanced therapeutic effectiveness.
  • Re-expression of the dopamine D(2) receptor increases apoptosis in pituitary tumor cells when treated with a receptor agonist.

Conclusions:

  • Epigenetic drugs offer a promising strategy for managing various tumor types, including pituitary tumors, by reversing gene silencing.
  • Combining DNMT and HDAC inhibitors enhances therapeutic outcomes.
  • These epigenetic modulators can identify novel, tumor-specific therapeutic targets and improve sensitivity to chemotherapy and radiotherapy.

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