Investigation of novel protein targets associated with metastatic uveal melanoma

Lead Researcher:

Prof Martin Clynes

Award Date:

1 January 2013

Host Institution:

Dublin City University

Scheme:

Health Research Award

Summary:

Uveal melanoma is the most common primary malignancy of the eye and accounts for 5% of all melanomas. If the primary tumour is small it is treated with eye-preserving radiation therapy; more commonly the tumours are quite large at presentation and are treated by removal of the eye. In approximately 4% of patients at initial diagnosis the disease has already spread to other organs and approximately 50% of patients will die of metastatic disease. In over 90% of patients with metastatic uveal melanoma the malignancy spreads to the liver; however the consequences are devastating and patients die within 6-9 months of diagnosis of metastatic disease. This is because no effective treatment currently exists for patients with metastatic uveal melanoma. There is an urgent need, therefore, for a greater understanding of the pathogenesis of uveal melanoma and the development of effective new therapies to treat these patients in order to prolong life. This project will apply exciting protein mass spectrometry technology to discover protein targets that play a role in the progression of uveal melanoma, and therefore may lead to the discovery of new therapies for treatment of metastatic disease. We will do this by comparing primary tumours from patients who did not develop metastatic disease with primary tumours from patients who did develop metastatic disease. Clinical samples from patients with uveal melanoma are being provided by the Royal Victoria Eye and Ear Hospital, to be analysed by the National Institute for Cellular Biotechnology at DCU. Novel differentially expressed protein targets will then be assessed for expression in primary tumour tissue sections (from patients with and without metastatic disease), and also analysed in cellular models to try to understand the functional role of these proteins and if they have the potential to be targets for drug treatment of metastatic disease.