Development of Coactivator-Dependent, First-in-Class Therapies for Breast Cancer

By integrating multiple signaling pathways that cancer cells rely on for growth and survival, p160 steroid receptor coactivator (SRC) family members (SRC-1, SRC-2/TIF2/GRIP1, SRC- 3/AIB1/pCIP/RAC3) represent emerging targets for anti-cancer drug development. During this reporting period, we have characterized and published our work on two potent and selective small molecule inhibitors (SMIs), bufalin and verrucarin A, against SRCs from high throughput screening efforts. Cryo-electron microscopic analyses of DNA/estrogen receptor/SRC-3 protein complexes achieved by our group are providing powerful new insights into understanding the conformation of intact, full length proteins in a complex and should provide valuable new information on the mechanism of action of SRC SMIs as well.
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