dc.contributor.author | Aleksic, T | |
dc.contributor.author | Verrill, C | |
dc.contributor.author | Bryant, RJ | |
dc.contributor.author | Han, C | |
dc.contributor.author | Worrall, AR | |
dc.contributor.author | Brureau, L | |
dc.contributor.author | Larré, S | |
dc.contributor.author | Higgins, GS | |
dc.contributor.author | Fazal, F | |
dc.contributor.author | Sabbagh, A | |
dc.contributor.author | Haider, S | |
dc.contributor.author | Buffa, FM | |
dc.contributor.author | Cole, D | |
dc.contributor.author | Macaulay, VM | |
dc.date.accessioned | 2021-06-11T12:31:57Z | |
dc.date.available | 2021-06-11T12:31:57Z | |
dc.date.issued | 2017-11-21 | |
dc.identifier.citation | British journal of cancer, 2017, 117 (11), pp. 1600 - 1606 | |
dc.identifier.issn | 0007-0920 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4627 | |
dc.identifier.eissn | 1532-1827 | |
dc.identifier.doi | 10.1038/bjc.2017.337 | |
dc.description.abstract | BACKGROUND: 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.format | Print-Electronic | |
dc.format.extent | 1600 - 1606 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | NATURE PUBLISHING GROUP | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Humans | |
dc.subject | Prostatic Neoplasms | |
dc.subject | Neoplasm Recurrence, Local | |
dc.subject | Receptor, IGF Type 1 | |
dc.subject | Neoplasm Staging | |
dc.subject | Aged | |
dc.subject | Middle Aged | |
dc.subject | Male | |
dc.title | IGF-1R associates with adverse outcomes after radical radiotherapy for prostate cancer. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2017-08-30 | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1038/bjc.2017.337 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by-nc-sa/4.0 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | British journal of cancer | |
pubs.issue | 11 | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR | |
pubs.publication-status | Published | |
pubs.volume | 117 | |
pubs.embargo.terms | Not known | |
dc.contributor.icrauthor | Haider, Syed | |