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    Manipulating the epigenome for the treatment of urological malignancies.

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    O'Rourke et al. (P&T 2013) ...
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    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.
    Issue Date
    2013-05
    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
    
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    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
    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
    ISSN
    1879-016X
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.pharmthera.2013.01.007
    Scopus Count
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    St. Luke's Radiation Oncology Network, Dublin

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