Activation of Src kinases through dimerization suggests novel therapeutic opportunities

ended

c-Src, the first proto-oncogene to be identified, controls many aspects of tumor biology including the capacity of the cancer cells to multiply, survive, and metastasize. We recently discovered that c-Src forms dimers and that dimerization is essential for the activity of the enzyme. This represents a significant paradigm shift in our understanding of the biology of Src family kinases, which until recently were assumed to function as monomeric proteins. The discovery that c-Src functions as a dimer creates the basis for development of a novel class therapeutics in principle based on disruption of Src dimerization. Our preliminary data indicate that such dimerization inhibitors have dramatic anti-tumor activity, suggesting that the proposed research may lead to development of an effective anti-cancer therapy. The project goal is to accomplish the following specific objectives: 1. To determine the efficacy of inhibition of Src myristoylation and dimerization for treatment of cancer; 2. To develop competitive inhibitors of Src dimerization and activity. The project will also create opportunities of boosting the research and innovation capacity of Europe, for obtaining IPRs, commercialization, and setting new collaborations with top US research institutions and companies. The proposal is intended as a career development fellowship that is designed to facilitate my reintegration into the EU science and to further my career towards a leading independent research position. I am confident that the quality and excellence of science produced and the new research and complementary skills obtained during the fellowship will serve as a cornerstone for my future career advancement and mark the beginning of my new laboratory and research program.