Abstract C162: MET oncogen inhibition as a potentitial target for therapy of uveal melanoma

Abstract

Abstract Purpose: Uveal melanomas (UM), including choroidal, iris and ciliary body melanomas, are the most common intraocular malignancy in adult. The tumor spreads through a hematogenous route mostly to the liver in about 50% of the patients. Once metastatic, UMs are highly fatal and currently there is no available therapy for these tumors. Identifying novel therapy is crucial to improve the survival of these patients. The aim of this study is to investigate the utility of MET inhibition as a potential therapy for UM. Methods: The frequency of MET activation (phospho-MET expression) in UM was studied using immunohistochemistry in 46 tumors. The half maximum inhibitory concentration (IC50) of selective MET inhibitor SU11274 was assessed on the five UM cell lines using cell proliferation assay. Inhibition of MET activation in UM cells treated with the SU11274 was confirmed using Western blot analysis. Effect of MET inhibition on cell migration was also studied. Results: Our results showed that the majority (82.5%) of the 46 UM studied showed strong to moderate expression of phospho-MET. Selective MET blocking showed inhibition of tumor cell proliferation at an IC50 ranging from 2∼ 10 µM. In addition significant inhibition UM cell line migration was observed. Conclusions: Our results indicate that MET is activated in a significant number of uveal melanomas. Our results also indicate the potential utility of MET inhibition as a target for therapy of UM. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):C162.