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Functional validation of “druggable” targets in uveal melanoma

Dr Sarah Lake

Collaborators:

Prof. Sarah Coupland
Prof. Bertil Damato
Prof. Heinrich Heimann
Dr Helen Kalirai
Prof. Ian Prior

Summary

Whole exome next generation sequencing of primary uveal melanomas revealed recurrent gene mutations.

This study will validate which of the mutated genes functionally regulate UM cell behaviour and how this is mediated. This will be achieved by determining the:

a) Frequency of mutations, and the expression of the corresponding protein, in a large independent cohort of UM.

b) Influence of the mutations on key aspects of UM cell behaviour (e.g. proliferation and apoptosis).

c) Molecular mechanisms underpinning mutated protein activity.

Key signalling pathways identified in this study are likely to be excellent “druggable” targets either through: the “re-purposing” of already available drugs; or, the development of novel therapeutics. Thus, new personalised treatment regimens will be available to UM patients to reduce their loss of vision, and mortality.

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