Brian J. Druker
Oregon Health & Science University
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Primary Section: 41, Medical Genetics, Hematology, and Oncology Membership Type:
Member
(elected 2007)
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Research Interests
As a translational researcher and medical oncologist, I have studied activated tyrosine kinases and their role in signal transduction and cellular transformation and the application of this knowledge to cancer therapies. The BCR-ABL oncogene is our primary model system because of its central role in the pathogenesis of a human disease, chronic myeloid leukemia (CML). As ABL tyrosine kinase activity is required for transformation by BCR-ABL, we evaluated a specific inhibitor of the ABL protein tyrosine kinase as a therapeutic agent for CML. This work identified imatinib (Gleevec) as having significant activity in pre-clinical and clinical studies, which led to it becoming the standard therapy for this disease. Additional pre-clinical profiling of this drug identified gastrointestinal stromal tumors as another potential disease for which imatinib is now the standard treatment. Further, our profiling of tyrosine phosphorylated proteins in patients with CML and our evaluation of the structural basis of inhibition of ABL by imatinib allowed for the rapid identification of kinase mutations as the major cause of clinical resistance to imatinib. Using this information, we have evaluated several novel ABL inhibitors that are now available for patients with imatinib resistance. In related work, we are performing functional screens to identify other tyrosine kinases that may be therapeutic targets in other leukemias.
