| THE
ROLE OF IGIFR IN PROSTATE CANCER.
Ben Turney and Dr Valerie M Macauley John Radcliffe Hospital, University of Oxford |
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Objectives:
In many patients with prostate cancer the cancer spreads to the bones; causing pain, and inviting fractures. This advanced disease can be controlled by hormonal treatments. However all tumours eventually become hormone-resistant and there is no other effective treatment.
This group is looking at a protein, "insulin-like growth factor receptor" (IGFR); this enables cancer cells to grow and to resist killing. Prostate cancer cells make higher levels of this protein than normal prostate tissue.
Firstly, the researchers are trying to answer the question, "does IGFR contribute to hormone resistance?". Secondly, they are using a novel technique called "gene silencing" to block IGFR production by prostate cancer cells and to determine if this will inhibit the growth of prostate cancer in experimental models. The latter aspect is particularly exciting and we await further reports with great interest.
Conclusions and Future Work:
The IGF1R immunohistochemistry results demonstrated that the IGF1R remains up-regulated in prostate tissue following androgen-independence and metastasis and is thus an important target for prostate cancer therapy. This work is the first study of serial expression levels of the IGF1R, and will form the basis of future studies investigating the levels of activated IGF1R antibody using phospho-IGF1R antibodies and activated downstream signalling proteins. Accurate analysis of the IGF1R and signalling status in prostate tissue will be essential to assess the pharmacodynamic effects of any IGF1R targeted therapy.
The work on small molecule inhibitors demonstrated inhibition of IGF1R phosphorylation inhibitory effects on signalling and growth. Further work is required to investigate their specificity for the IGF1R and effects in vivo.
Only recently has it been feasible to target the IGF1R with specific or selective small molecule inhibitors. Results presented here and in other reports (Garcia-Echeverria et al., 2004; Warchamana-Greene et al., 2005) have provided evidence pave the way for clinical trials with small molecule inhibitors and other strategies that target the IGF1R. Within the next year, clinical studies of IGF1R antibodies and inhibitors will commence at the CRUK Medical Oncology Unit at the Churchill, and will provide the opportunity for us to exploit the knowledge gained in this research study.
Thus this is a very exciting time for IGF research, and we are grateful to Prostate UK for supporting this work, which has allowed us to explore the potential therapeutic benefits of targeting the IGF axis in prostate cancer.
Read the full Final Report on this research here (.pdf 374Kb).
Summary of final research report dated 29 February 2008
Project 2004/05