Manipulating the epigenome for the treatment of urological malignancies.

Hdl Handle:
http://hdl.handle.net/10147/323772
Title:
Manipulating the epigenome for the treatment of urological malignancies.
Authors:
O'Rourke, Colm J; Knabben, Vinicius; Bolton, Eva; Moran, Diarmaid; Lynch, Thomas; Hollywood, Donal; Perry, Antoinette S
Affiliation:
Prostate Molecular Oncology, Institute of Molecular Medicine, Trinity College, Dublin, Ireland.
Citation:
O'Rourke CJ et al. Manipulating the epigenome for the treatment of urological malignancies. Pharmacol. Ther. 2013, 138 (2):185-96
Journal:
Pharmacology & therapeutics
Issue Date:
May-2013
URI:
http://hdl.handle.net/10147/323772
DOI:
10.1016/j.pharmthera.2013.01.007
PubMed ID:
23353098
Abstract:
Urological malignancies (cancers of the prostate, bladder, kidney and testes) account for 15% of all human cancers and more than 500,000 deaths worldwide each year. This group of malignancies is spread across multiple generations, affecting the young (testicular) through middle and old-age (kidney, prostate and bladder). Like most human cancers, urological cancers are characterized by widespread epigenetic insult, causing changes in DNA hypermethylation and histone modifications leading to silencing of tumor suppressor genes and genomic instability. The inherent stability yet dynamic plasticity of the epigenome lends itself well to therapeutic manipulation. Epigenetic changes are amongst the earliest lesions to occur during carcinogenesis and are essentially reversible (unlike mutations). For this reason, much attention has been placed over the past two decades on deriving pharmacological compounds that can specifically target and reverse such epi-mutations, either halting cancer on its developmental trajectory or reverting fully formed cancers to a more clinically manageable state. This review discusses DNA methyltransferase and histone deacetylase inhibitors that have been extensively studied in preclinical models and clinical trials for advanced and metastatic urological cancers.
Item Type:
Article
Language:
en
Keywords:
CANCER; GENETICS
Local subject classification:
UROLOGY
MeSH:
Antineoplastic Agents; DNA Methylation; DNA Modification Methylases; Epigenesis, Genetic; Histone Deacetylase Inhibitors; Histone Deacetylases; Humans; Male; Urologic Neoplasms
ISSN:
1879-016X

Full metadata record

DC FieldValue Language
dc.contributor.authorO'Rourke, Colm Jen_GB
dc.contributor.authorKnabben, Viniciusen_GB
dc.contributor.authorBolton, Evaen_GB
dc.contributor.authorMoran, Diarmaiden_GB
dc.contributor.authorLynch, Thomasen_GB
dc.contributor.authorHollywood, Donalen_GB
dc.contributor.authorPerry, Antoinette Sen_GB
dc.date.accessioned2014-07-24T14:29:54Z-
dc.date.available2014-07-24T14:29:54Z-
dc.date.issued2013-05-
dc.identifier.citationO'Rourke CJ et al. Manipulating the epigenome for the treatment of urological malignancies. Pharmacol. Ther. 2013, 138 (2):185-96en_GB
dc.identifier.issn1879-016X-
dc.identifier.pmid23353098-
dc.identifier.doi10.1016/j.pharmthera.2013.01.007-
dc.identifier.urihttp://hdl.handle.net/10147/323772-
dc.description.abstractUrological malignancies (cancers of the prostate, bladder, kidney and testes) account for 15% of all human cancers and more than 500,000 deaths worldwide each year. This group of malignancies is spread across multiple generations, affecting the young (testicular) through middle and old-age (kidney, prostate and bladder). Like most human cancers, urological cancers are characterized by widespread epigenetic insult, causing changes in DNA hypermethylation and histone modifications leading to silencing of tumor suppressor genes and genomic instability. The inherent stability yet dynamic plasticity of the epigenome lends itself well to therapeutic manipulation. Epigenetic changes are amongst the earliest lesions to occur during carcinogenesis and are essentially reversible (unlike mutations). For this reason, much attention has been placed over the past two decades on deriving pharmacological compounds that can specifically target and reverse such epi-mutations, either halting cancer on its developmental trajectory or reverting fully formed cancers to a more clinically manageable state. This review discusses DNA methyltransferase and histone deacetylase inhibitors that have been extensively studied in preclinical models and clinical trials for advanced and metastatic urological cancers.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to Pharmacology & therapeuticsen_GB
dc.subjectCANCERen_GB
dc.subjectGENETICSen_GB
dc.subject.meshAntineoplastic Agents-
dc.subject.meshDNA Methylation-
dc.subject.meshDNA Modification Methylases-
dc.subject.meshEpigenesis, Genetic-
dc.subject.meshHistone Deacetylase Inhibitors-
dc.subject.meshHistone Deacetylases-
dc.subject.meshHumans-
dc.subject.meshMale-
dc.subject.meshUrologic Neoplasms-
dc.subject.otherUROLOGYen_GB
dc.titleManipulating the epigenome for the treatment of urological malignancies.en_GB
dc.typeArticleen
dc.contributor.departmentProstate Molecular Oncology, Institute of Molecular Medicine, Trinity College, Dublin, Ireland.en_GB
dc.identifier.journalPharmacology & therapeuticsen_GB
dc.description.fundingNo fundingen
dc.description.provinceLeinsteren
dc.description.peer-reviewpeer-reviewen

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