Development of Specific Inhibitors for Breast Cancer-Associated Variants of ErbB2
Annual rept. 26 Sep 2014 - 25 Sep 2015
STATE UNIV OF NEW YORK AT STONY BROOK RESEARCH FOUNDATION
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The receptor tyrosine kinase HER2ErbB2 is one of the most highly mutated tyrosine kinases in breast cancer. Several mutations within the ErbB2 kinase domain have been identified in breast cancer patients, but in most cases it is not known whether these mutations increase kinase activity and signaling. The first goal of this project is to provide data linking the mutations to their degree of kinase activation. In the first year of this project, we have expressed and purified the wild-type ErbB2 kinase domain and four cancer-associated mutants, one of which G776C has not previously been reported. We have developed a kinase assay to be used in inhibitor screening. All four mutants are hyperactivated relative to wild-type ErbB2, as assessed by in vitro kinase assays and cellular assays. In the next phase of the project, we will screen inhibitors identified by our collaborator, Dr. Robert Rizzo.
- Medicine and Medical Research