Radiation Sensitization in Breast Cancer via Targeting Survivin Expression
Annual rept. 20 Apr 2004-19 Apr 2005
VANDERBILT UNIV NASHVILLE TN
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We proposed to determine whether overexpression- of surviving results in radio resistance and the possible mechanisms whether irradiation down regulates p34CDC2 and its mechanism in vascular endothelium and whether CDK cyclin dependent kinase inhibitors sensitize it to radiation injury the mechanism of surviving- deregulation in breast cancer and whether inhibition of surviving or its regulator, p34CDC2 abolishes radio resistance. We found that overexpression of surviving leads to radiation resistance and CDK inhibitors result in radiosensitization. We also found that deregulation of surviving in breast cancer is mediated by Stat3 Signal transducer and activator of transcription. Co-inhibition of surviving and Stat3 results in significantly increased sensitization of breast cancer. In the next two years, we will determine the biological significance of combining surviving inhibitors or CDK inhibitors with radiotherapy in xenograft models of breast cancer. The proposed study will address the biological basis of combining radio therapy with inhibitors of surviving or CDK in - the treatment of locally advanced breast cancer.
- Anatomy and Physiology
- Medicine and Medical Research