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dc.contributor.authorCrespo, Men_US
dc.contributor.authorvan Dalum, Gen_US
dc.contributor.authorFerraldeschi, Ren_US
dc.contributor.authorZafeiriou, Zen_US
dc.contributor.authorSideris, Sen_US
dc.contributor.authorLorente, Den_US
dc.contributor.authorBianchini, Den_US
dc.contributor.authorRodrigues, DNen_US
dc.contributor.authorRiisnaes, Ren_US
dc.contributor.authorMiranda, Sen_US
dc.contributor.authorFigueiredo, Ien_US
dc.contributor.authorFlohr, Pen_US
dc.contributor.authorNowakowska, Ken_US
dc.contributor.authorde Bono, JSen_US
dc.contributor.authorTerstappen, LWMMen_US
dc.contributor.authorAttard, Gen_US
dc.date.accessioned2020-07-28T13:29:30Z
dc.date.issued2015-03-31en_US
dc.identifier.citationBritish journal of cancer, 2015, 112 (7), pp. 1166 - 1174en_US
dc.identifier.issn0007-0920en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3878
dc.identifier.eissn1532-1827en_US
dc.identifier.doi10.1038/bjc.2015.63en_US
dc.description.abstractBACKGROUND:Abiraterone and enzalutamide are novel endocrine treatments that abrogate androgen receptor (AR) signalling in castration-resistant prostate cancer (CRPC). Here, we developed a circulating tumour cells (CTCs)-based assay to evaluate AR expression in real-time in CRPC and investigated nuclear AR expression in CTCs in patients treated with enzalutamide and abiraterone. METHODS:CTCs were captured and characterised using the CellSearch system. An automated algorithm to identify CTCs and quantify AR expression was employed. The primary aim was to evaluate the association between CTC AR expression and prior treatment with abiraterone or enzalutamide. RESULTS:AR expression in CTCs was evaluated in 94 samples from 48 metastatic CRPC patients. We observed large intra-patient heterogeneity of AR expression in CTCs. Prior exposure to abiraterone or enzalutamide was not associated with a change in CTCs AR expression (median intensity and distribution of AR-positive classes). In support of this, we also confirmed maintained nuclear AR expression in tissue samples collected after progression on abiraterone. AR staining also identified additional AR-positive CD45-negative circulating cells that were CK-negative/weak and therefore missed using standard protocols. The number of these events correlated with traditional CTCs and was associated with worse outcome on univariate analysis. CONCLUSIONS:We developed a non-invasive method to monitor AR nuclear expression in CTCs. Our studies confirm nuclear AR expression in CRPC patients progressing on novel endocrine treatments. Owing to the significant heterogeneity of AR expression in CTCs, studies in larger cohorts of patients are required to identify associations with outcome.en_US
dc.formatElectronicen_US
dc.format.extent1166 - 1174en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttps://creativecommons.org/licenses/by-nc-sa/4.0en_US
dc.subjectCell Line, Tumoren_US
dc.subjectHumansen_US
dc.subjectNeoplasm Metastasisen_US
dc.subjectDisease Progressionen_US
dc.subjectPhenylthiohydantoinen_US
dc.subjectAndrostenesen_US
dc.subjectReceptors, Androgenen_US
dc.subjectAdulten_US
dc.subjectAgeden_US
dc.subjectAged, 80 and overen_US
dc.subjectMiddle Ageden_US
dc.subjectMaleen_US
dc.subjectNeoplastic Cells, Circulatingen_US
dc.subjectProstatic Neoplasms, Castration-Resistanten_US
dc.titleAndrogen receptor expression in circulating tumour cells from castration-resistant prostate cancer patients treated with novel endocrine agents.en_US
dc.typeJournal Article
dcterms.dateAccepted2015-01-27en_US
rioxxterms.versionofrecord10.1038/bjc.2015.63en_US
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by-nc-sa/4.0en_US
rioxxterms.licenseref.startdate2015-03-31en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfBritish journal of canceren_US
pubs.issue7en_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Cancer Biomarkers
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Cancer Biomarkers
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Treatment Resistance
pubs.publication-statusPublisheden_US
pubs.volume112en_US
pubs.embargo.termsNot knownen_US
icr.researchteamCancer Biomarkersen_US
icr.researchteamProstate Cancer Targeted Therapy Groupen_US
icr.researchteamTreatment Resistanceen_US
dc.contributor.icrauthorDe Bono, Johannen_US
dc.contributor.icrauthorAttard, Gerhardten_US
dc.contributor.icrauthorCrespo, Mateusen_US
dc.contributor.icrauthorMiranda, Susanaen_US


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https://creativecommons.org/licenses/by-nc-sa/4.0
Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by-nc-sa/4.0