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

Autor: Aleksic T; Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, UK., Verrill C; Department of Cellular Pathology, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford OX3 9DU UK.; Nuffield Department of Surgical Sciences, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK., Bryant RJ; Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, UK.; Nuffield Department of Surgical Sciences, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK., Han C; Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, UK.; Oxford Cancer and Haematology Centre, Oxford University Hospitals NHS Foundation Trust, Churchill Hospital, Oxford OX3 7LJ, UK., Worrall AR; Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, UK., Brureau L; Nuffield Department of Surgical Sciences, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK., Larré S; Nuffield Department of Surgical Sciences, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK., Higgins GS; Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, UK.; Oxford Cancer and Haematology Centre, Oxford University Hospitals NHS Foundation Trust, Churchill Hospital, Oxford OX3 7LJ, UK., Fazal F; Oxford Cancer and Haematology Centre, Oxford University Hospitals NHS Foundation Trust, Churchill Hospital, Oxford OX3 7LJ, UK., Sabbagh A; Oxford Cancer and Haematology Centre, Oxford University Hospitals NHS Foundation Trust, Churchill Hospital, Oxford OX3 7LJ, UK., Haider S; Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, UK., Buffa FM; Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, UK., Cole D; Oxford Cancer and Haematology Centre, Oxford University Hospitals NHS Foundation Trust, Churchill Hospital, Oxford OX3 7LJ, UK., Macaulay VM; Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, UK.; Oxford Cancer and Haematology Centre, Oxford University Hospitals NHS Foundation Trust, Churchill Hospital, Oxford OX3 7LJ, UK.
Jazyk: angličtina
Zdroj: British journal of cancer [Br J Cancer] 2017 Nov 21; Vol. 117 (11), pp. 1600-1606. Date of Electronic Publication: 2017 Oct 03.
DOI: 10.1038/bjc.2017.337
Abstrakt: 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.
Databáze: MEDLINE
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