Identification of the Microtubule-Inhibitor Activated Bcl-xL Kinase: A Regulator of Breast Cancer Cell Chemosensitivity to Taxol

摘要

This predoctoral fellowship supported research on apoptotic signaling in response to key breast cancer chemotherapeutics, microtubule inhibitor (MTI). The funding also supported educational activities that trained the Principal Investigator (PI) as a physician-scientist. MTIs are the most actively used agents for metastatic and adjuvant breast cancer therapy, yet their use is limited by resistance and side effects. MTIs activate a kinase that phosphorylates and inactivates Bcl-xL, an anti-apoptotic protein that can cause resistance to chemotherapeutic agents. Overall, our data show that Cdk1/cyclin B1 phosphorylates Bcl-xL in vitro and cell culture models following MTI treatment, during normal mitosis, and during prolonged mitosis without MTI treatment. Published data also indicate that Bcl-xL phosphorylation increases tumor cell apoptosis. Presented here are the final data on the clinical research study of Bcl-xL and Bcl-2 phosphorylation pre- and post-taxane treatment in patients who have breast cancer. Remaining research and educational activities are discussed.