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dc.contributor.authorAleksic, T
dc.contributor.authorVerrill, C
dc.contributor.authorBryant, RJ
dc.contributor.authorHan, C
dc.contributor.authorWorrall, AR
dc.contributor.authorBrureau, L
dc.contributor.authorLarré, S
dc.contributor.authorHiggins, GS
dc.contributor.authorFazal, F
dc.contributor.authorSabbagh, A
dc.contributor.authorHaider, S
dc.contributor.authorBuffa, FM
dc.contributor.authorCole, D
dc.contributor.authorMacaulay, VM
dc.date.accessioned2021-06-11T12:31:57Z
dc.date.available2021-06-11T12:31:57Z
dc.date.issued2017-11-21
dc.identifier.citationBritish journal of cancer, 2017, 117 (11), pp. 1600 - 1606
dc.identifier.issn0007-0920
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4627
dc.identifier.eissn1532-1827
dc.identifier.doi10.1038/bjc.2017.337
dc.description.abstractBACKGROUND: Activated type 1 insulin-like growth factor receptors (IGF-1Rs) undergo internalisation and nuclear translocation, promoting cell survival. We previously reported that IGF-1R inhibition delays DNA damage repair, sensitising prostate cancer cells to ionising radiation. Here we tested the clinical relevance of these findings. METHODS: We assessed associations between IGF-1R and clinical outcomes by immunohistochemistry in diagnostic biopsies of 136 men treated with 55-70 Gy external beam radiotherapy for prostate cancer, comparing results with publicly available transcriptional data in surgically treated patients. RESULTS: Following radiotherapy, overall recurrence-free survival was shorter in patients whose tumours contained high total, cytoplasmic and internalised (nuclear/cytoplasmic) IGF-1R. High total IGF-1R associated with high primary Gleason grade and risk of metastasis, and cytoplasmic and internalised IGF-1R with biochemical recurrence, which includes patients experiencing local recurrence within the radiation field indicating radioresistance. In multivariate analysis, cytoplasmic, internalised and total IGF-1R were independently associated with risk of overall recurrence, and cytoplasmic IGF-1R was an independent predictor of biochemical recurrence post radiotherapy. Insulin-like growth factor receptors expression did not associate with biochemical recurrence after radical prostatectomy. CONCLUSIONS: These data reveal increased risk of post-radiotherapy recurrence in men whose prostate cancers contain high levels of total or cytoplasmic IGF-1R.
dc.formatPrint-Electronic
dc.format.extent1600 - 1606
dc.languageeng
dc.language.isoeng
dc.publisherNATURE PUBLISHING GROUP
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectHumans
dc.subjectProstatic Neoplasms
dc.subjectNeoplasm Recurrence, Local
dc.subjectReceptor, IGF Type 1
dc.subjectNeoplasm Staging
dc.subjectAged
dc.subjectMiddle Aged
dc.subjectMale
dc.titleIGF-1R associates with adverse outcomes after radical radiotherapy for prostate cancer.
dc.typeJournal Article
dcterms.dateAccepted2017-08-30
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1038/bjc.2017.337
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by-nc-sa/4.0
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfBritish journal of cancer
pubs.issue11
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR
pubs.publication-statusPublished
pubs.volume117
pubs.embargo.termsNot known
dc.contributor.icrauthorHaider, Syed


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