• Login
    View Item 
    •   Home
    • The Christie Research Publications Repository
    • All Christie Publications
    • View Item
    •   Home
    • The Christie Research Publications Repository
    • All Christie Publications
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of ChristieCommunitiesTitleAuthorsIssue DateSubmit DateSubjectsThis CollectionTitleAuthorsIssue DateSubmit DateSubjectsProfilesView

    My Account

    LoginRegister

    Local Links

    The Christie WebsiteChristie Library and Knowledge Service

    Statistics

    Display statistics

    Bad neighbours: hypoxia and genomic instability in prostate cancer

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    bjr bad.pdf
    Size:
    1.362Mb
    Format:
    PDF
    Description:
    UNPAYWALL
    Download
    Authors
    Ashton, Jack
    Bristow, Robert G
    Affiliation
    Translational Oncogenomics, CRUK Manchester Institute and CRUK Manchester Centre, Manchester,
    Issue Date
    2020
    
    Metadata
    Show full item record
    Abstract
    Prostate cancer (PCa) is a clinically heterogeneous disease and has poor patient outcome when tumours progress to castration-resistant and metastatic states. Understanding the mechanistic basis for transition to late stage aggressive disease is vital for both assigning patient risk status in the localised setting and also identifying novel treatment strategies to prevent progression. Subregions of intratumoral hypoxia are found in all solid tumours and are associated with many biologic drivers of tumour progression. Crucially, more recent findings show the co-presence of hypoxia and genomic instability can confer a uniquely adverse prognosis in localised PCa patients. In-depth informatic and functional studies suggests a role for hypoxia in co-operating with oncogenic drivers (e.g. loss of PTEN) and suppressing DNA repair capacity to alter clonal evolution due to an aggressive mutator phenotype. More specifically, hypoxic suppression of homologous recombination represents a 'contextual lethal' vulnerability in hypoxic prostate tumours which could extend the application of existing DNA repair targeting agents such as poly-ADP ribose polymerase inhibitors. Further investigation is now required to assess this relationship on the background of existing genomic alterations relevant to PCa, and also characterise the role of hypoxia in driving early metastatic spread. On this basis, PCa patients with hypoxic tumours can be better stratified into risk categories and treated with appropriate therapies to prevent progression.
    Citation
    Ashton J, Bristow R. Bad neighbours: hypoxia and genomic instability in prostate cancer. The British journal of radiology. 2020:20200087.
    Journal
    British Journal of Radiology
    URI
    http://hdl.handle.net/10541/623063
    DOI
    10.1259/bjr.20200087
    PubMed ID
    32551913
    Additional Links
    https://dx.doi.org/10.1259/bjr.20200087
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1259/bjr.20200087
    Scopus Count
    Collections
    All Christie Publications

    entitlement

    Related articles

    • Intratumoral hypoxia as the genesis of genetic instability and clinical prognosis in prostate cancer.
    • Authors: Taiakina D, Dal Pra A, Bristow RG
    • Issue date: 2014
    • Combined MYC Activation and Pten Loss Are Sufficient to Create Genomic Instability and Lethal Metastatic Prostate Cancer.
    • Authors: Hubbard GK, Mutton LN, Khalili M, McMullin RP, Hicks JL, Bianchi-Frias D, Horn LA, Kulac I, Moubarek MS, Nelson PS, Yegnasubramanian S, De Marzo AM, Bieberich CJ
    • Issue date: 2016 Jan 15
    • A Prostate Cancer "Nimbosus": Genomic Instability and SChLAP1 Dysregulation Underpin Aggression of Intraductal and Cribriform Subpathologies.
    • Authors: Chua MLK, Lo W, Pintilie M, Murgic J, Lalonde E, Bhandari V, Mahamud O, Gopalan A, Kweldam CF, van Leenders GJLH, Verhoef EI, Hoogland AM, Livingstone J, Berlin A, Dal Pra A, Meng A, Zhang J, Orain M, Picard V, Hovington H, Bergeron A, Lacombe L, Fradet Y, Têtu B, Reuter VE, Fleshner N, Fraser M, Boutros PC, van der Kwast TH, Bristow RG
    • Issue date: 2017 Nov
    • "Contextual" synthetic lethality and/or loss of heterozygosity: tumor hypoxia and modification of DNA repair.
    • Authors: Chan N, Bristow RG
    • Issue date: 2010 Sep 15
    • Recent Advances in DNA Repair Pathway and Its Application in Personalized Care of Metastatic Castration-Resistant Prostate Cancer (mCRPC).
    • Authors: Xu C, Mao S, Jiang H
    • Issue date: 2020
    DSpace software (copyright © 2002 - 2025)  DuraSpace
    Quick Guide | Contact Us
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.