| The pituitary tumour epigenome: aberrations and prospects for targeted therapy. | |
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MedLine Citation:
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PMID: 22525730 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Global and gene-specific changes in the epigenome are hallmarks of most tumour types, including those of pituitary origin. In contrast to genetic mutations, epigenetic changes (aberrant DNA methylation and histone modifications) are potentially reversible. Drugs that specifically target or inhibit DNA methyltransferases (DNMTs) and histone deacetylases (HDACs) can be used to restore the expression of epigenetically silenced genes. These drugs can potentially increase the sensitivity of tumour cells to conventional treatment modalities, such as chemotherapy and radiotherapy. Drug-induced reversal of transcriptional silencing can also be used to restore dopamine-D(2)-receptor-negative, hormone-refractory tumours to their previous receptor-positive, hormone-responsive status. Synergy between HDAC and DNMT inhibitors makes these pharmacological agents more therapeutically effective when administered in combination than when used alone. Studies in pituitary tumour cell lines show that drug-induced re-expression of the epigenetically silenced dopamine D(2) receptor leads to an increase in apoptosis mediated by a receptor agonist. Collectively, the use of drugs to directly or indirectly reverse gene-specific epigenetic changes, in combination with conventional therapeutic interventions, has potential for the clinical management of multiple tumour types-including those of pituitary origin. Furthermore, these drugs can be used to identify epigenetically regulated genes that could be novel, tumour-specific therapeutic targets. |
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Authors:
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Kiren Yacqub-Usman; Alan Richardson; Cuong V Duong; Richard N Clayton; William E Farrell |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-4-24 |
Journal Detail:
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Title: Nature reviews. Endocrinology Volume: - ISSN: 1759-5037 ISO Abbreviation: - Publication Date: 2012 Apr |
Date Detail:
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Created Date: 2012-4-24 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101500078 Medline TA: Nat Rev Endocrinol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Human Disease and Genomics Group, Institute of Science and Technology in Medicine, School of Medicine, Keele University, Stoke-on-Trent, Staffordshire ST4 7QB, UK. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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