Herceptin-Resistance and Overexpression of Anti-Apoptotic Molecule Bcl-XL: a Potential Strategy for Overcoming Resistance to Herceptin

Abstract

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-2/neu(+) 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.

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Document Details

Document Type
Technical Report
Publication Date
Jul 01, 2006
Accession Number
ADA464017

Entities

People

  • Liang Xu

Organizations

  • University of Michigan

Tags

DTIC Thesaurus Topics

  • Breast Cancer
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Chemotherapeutic Agents
  • Chemotherapy
  • Clinical Trials
  • Drug Combinations
  • Drug Therapy
  • Gene Therapy
  • Molecules
  • Neoplasms
  • Patent Applications
  • Small Molecules
  • Therapy
  • Three Dimensional
  • Tumor Cell Line

Fields of Study

  • Biology
  • Chemistry
  • Medicine

Readers

  • Aviation Safety and Air Traffic Management
  • Oncology