RGD Reference Report - IGF-1R associates with adverse outcomes after radical radiotherapy for prostate cancer. - Rat Genome Database

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IGF-1R associates with adverse outcomes after radical radiotherapy for prostate cancer.

Authors: Aleksic, Tamara  Verrill, Clare  Bryant, Richard J  Han, Cheng  Worrall, Andrew Ross  Brureau, Laurent  Larré, Stephane  Higgins, Geoff S  Fazal, Fahad  Sabbagh, Ahmad  Haider, Syed  Buffa, Francesca M  Cole, David  Macaulay, Valentine M 
Citation: Aleksic T, etal., Br J Cancer. 2017 Nov 21;117(11):1600-1606. doi: 10.1038/bjc.2017.337. Epub 2017 Oct 3.
RGD ID: 13504752
Pubmed: PMID:28972962   (View Abstract at PubMed)
PMCID: PMC5729437   (View Article at PubMed Central)
DOI: DOI:10.1038/bjc.2017.337   (Journal Full-text)


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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
prostate cancer disease_progressionIEP 13504752 RGD 
prostate cancer disease_progressionISOIGF1R (Homo sapiens)13504752; 13504752 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Igf1r  (insulin-like growth factor 1 receptor)

Genes (Mus musculus)
Igf1r  (insulin-like growth factor I receptor)

Genes (Homo sapiens)
IGF1R  (insulin like growth factor 1 receptor)


Additional Information