Journal
NATURE REVIEWS DRUG DISCOVERY
Volume 6, Issue 7, Pages 540-555Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nrd2221
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The involvement of the RAS superfamily of monomeric GTPases in carcinogenesis is increasingly being appreciated. A complex array of post-translational modifications and a highly sophisticated protein network regulate the spatio-temporal activation of these GTPases. Previous attempts to pharmacologically target this family have focused on the development of farnesyltransferase inhibitors, but the performance of such agents in cancer clinical trials has not been as good as hoped. Here, we review emerging druggable targets and novel therapeutic approaches targeting prenylation and post-prenylation modifications and the functional regulation of GDP/GTP exchange as exciting alternatives for anticancer therapy.
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