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David Cheresh, UCSD to Speak at 8th Protein Kinases Conference on July 8-9 in Boston, Massachusetts - David Cheresh, Distinguished Professor and Vice-Chair for Research and Development at the University of California San Diego, will give a keynote presentation at the 8th Protein Kinases in Drug Discovery Conference on July 8-9, 2013 in Boston, MA
David Cheresh, UCSD to Speak at 8th Protein Kinases Conference on July 8-9 in Boston, Massachusetts

 

NewswireToday - /newswire/ - Monrovia, CA, United States, 2013/05/07 - David Cheresh, Distinguished Professor and Vice-Chair for Research and Development at the University of California San Diego, will give a keynote presentation at the 8th Protein Kinases in Drug Discovery Conference on July 8-9, 2013 in Boston, MA.

   
 
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David Cheresh, Distinguished Professor and Vice-Chair for Research and Development at the University of California San Diego, will give a keynote presentation on “Overcoming Cancer Cell Resistance to Receptor Tyrosine Kinase Inhibitors” at the 8th Protein Kinases in Drug Discovery Conference on July 8-9, 2013 in Boston, MA.

Tumor drug resistance limits the long-term success of therapies targeting EGFR. Here, we identify integrin αvβ3 as a biomarker of intrinsic and acquired resistance to erlotinib in human pancreatic and lung carcinomas irrespective of their KRAS mutational status. Functionally, αvβ3 is necessary and sufficient for this resistance where it acts in the unligated state as a scaffold to recruit active KRAS into membrane clusters switching tumor dependency from EGFR to KRAS. The KRAS effector RalB is recruited to this complex, where it mediates erlotinib resistance via a TBK-1/NF-κB pathway. Disrupting assembly of this complex or inhibition of its downstream effectors fully restores tumor sensitivity to EGFR blockade. Dr. Cheresh and his team’s findings uncouple KRAS mutations from erlotinib resistance, revealing an unexpected requirement for integrin αvβ3 in this process.

David Cheresh studies the mechanism of action of signaling networks that regulate tumor growth, stemness, drug resistance and metastasis. He discovered the avb3 integrin is a functional marker of angiogenic blood vessels. His work is basic and translational focusing 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’s research in this area has been widely cited with seven of his peer-reviewed publications being cited >1000 times. 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.

To remain competitive in the kinase field, stay abreast with recent development trends and technological advancements aimed towards challenges which accompany the development of ATP-competitive kinase inhibitors and problems of gatekeeper-associated drug resistance. GTC’s 8th Protein Kinases in Drug Discovery Conference will provide an overview of the preclinical development of kinase inhibitors for cancers and inflammatory diseases. Key highlights include discussions on how phenotypic screening can be used for the identification of novel kinase targets and profiling, challenges and limitations of phenotypic screening, the use of physiologically relevant assays, structure-based drug design and cheminformatics tools, as well as strategies to develop selective inhibitors by targeting target inactive and active (DFG-out/in) kinases.

 
 
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Written by / Agency / Source: GTCbio - Biopharmaceutical Conference

 
 

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David Cheresh, UCSD to Speak at 8th Protein Kinases Conference on July 8-9 in Boston, Massachusetts

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