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2012 Featured Talks » Cilengitide, from Discovery to Clinical Development and Back

Cilengitide, from Discovery to Clinical Development and Back

David Cheresh, PhD, Moores Cancer Center

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David Cheresh studies the mechanism of action of signaling networks that regulate cancer growth and metastasis and focuses on new strategies for biologically-based drug development. In particular, he studies how integrins and growth factor receptors promote, cell survival, angiogenesis and tumor invasion. His work has lead to the development of several drugs now in various stages of clinical development. Cheresh together with scientists at Applied Molecular Evolution developed a humanized antibody (Vitaxin) directed to integrin avb3 which is now being developed by Astra Zeneca. In collaboration with Merck Darmstadt, Cheresh developed an integrin antagonist (Cilengitide) targeting integrins avb3 and avb5 that has now produced significant survival benefit in glioblastoma patients and has lead to the first integrin targeted drug to enter Phase III clinical trials for cancer. David Cheresh was the scientific founder of TargeGen a San Diego based biotechnology company which developed a number of small molecules based in part on discoveries made in the Cheresh laboratory. Recently, TargeGen was acquired by Sanofi Aventis who is developing a highly selective JAK2 inhibitor discovered by TargeGen scientists. Most recently, Cheresh and his colleagues have developed a novel scaffold based chemistry approach to stabilize kinases in their inactive state. These studies have lead to the discovery of a first in class Raf inhibitor that has distinct advantages relative to ATP mimetics of RAF. Cheresh and his colleagues at UCSD have founded a new start up company (Amitech Therapeutic Solutions, ATS) which focuses on the discovery of allosteric inhibitors of kinases such as those targeting Raf and other important molecules/pathways relevant to cancer and inflammatory disease.