Show simple item record

dc.contributor.authorAshton, Jack
dc.contributor.authorBristow, Robert G
dc.date.accessioned2020-08-10T08:09:15Z
dc.date.available2020-08-10T08:09:15Z
dc.date.issued2020en
dc.identifier.citationAshton J, Bristow R. Bad neighbours: hypoxia and genomic instability in prostate cancer. The British journal of radiology. 2020:20200087.en
dc.identifier.pmid32551913en
dc.identifier.doi10.1259/bjr.20200087en
dc.identifier.urihttp://hdl.handle.net/10541/623063
dc.description.abstractProstate 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.en
dc.language.isoenen
dc.relation.urlhttps://dx.doi.org/10.1259/bjr.20200087en
dc.titleBad neighbours: hypoxia and genomic instability in prostate canceren
dc.typeArticleen
dc.contributor.departmentTranslational Oncogenomics, CRUK Manchester Institute and CRUK Manchester Centre, Manchester,en
dc.identifier.journalBritish Journal of Radiologyen
dc.description.noteen]
refterms.dateFOA2020-08-12T08:57:21Z


Files in this item

Thumbnail
Name:
bjr bad.pdf
Size:
1.362Mb
Format:
PDF
Description:
UNPAYWALL

This item appears in the following Collection(s)

Show simple item record