Herceptin-Resistance and Overexpression of Anti-Apoptotic Molecule Bcl-XL: a Potential Strategy for Overcoming Resistance to Herceptin
Final rept. 1 Jul 2004-30 Jun 2006
MICHIGAN UNIV ANN ARBOR
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The major goal of this Concept Award project is to investigate whether a small molecule inhibitor of Bcl-xL will be able to overcome the Herceptin-resistance of Her-2neu breast cancer. Our hypothesis is that anti-apoptotic molecule Bcl-xL may play a role in Herceptin resistance, and a potent and specific Bcl-xL inhibitor might be able to block or even reverse this resistance, thus improving efficacy of Herceptin therapy. This is based on our basic hypothesis that Bcl-xL is the primary molecular target that mediate the anticancer activity of the small molecule Bcl-xL inhibitor, --gossypol, in human breast cancer cells. Our ultimate goal is to develop --gossypol as a novel molecular targeted therapy for the treatment of breast cancer with Bcl-xL overexpression. In this project, we investigated anti-tumor activity and the mechanism of action of --gossypol in human breast cancer with Bcl-xL overexpression, and investigate the potential synergistic effects of gossypol in combination with Herceptin therapy.
- Medicine and Medical Research