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Low Voltage Activated Calcium Channels - Their Role in HER2-Driven Breast Cancer and Potential as a New Therapeutic Target

Descriptive Note:

[Technical Report, Final Report]

Corporate Author:

The Rector and Visitors of the University of Virginia

Personal Author(s):

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Breast cancer is a devastating disease affecting both women and men, and despite many advancements it remains incurable when metastatic. Efficient novel treatments, or enhancements to current ones, are desperately needed to improve breast cancer therapy and extend patient lives. The overall goal of this proposal is to develop tumor specific, safe and effective therapy for breast cancer. We will concentrate on HER2-overexpressing tumors, which are diagnosed in one in four patients. Despite enormous progress in developing targeted therapies, such as the anti-HER2 antibodies, cancer cells eventually acquire resistance which clinically is manifested by tumor growthrecurrence in spite of targeted therapy. Currently HER2 targeted therapies achieve highest response rates when combined with chemotherapy but chemotherapy causes in undesirable side effects due to off-target effects on normal tissue which diminishes quality of life for the patient. A way to address this problem is to use a drug that either attacks only tumor cells or enhances the response of tumors but not normal tissues to current therapies. Such an approach enables the use of smaller doses to treat the tumor, resulting in fewer side effects. Our research shows that so called low voltage activated LVA calcium channels are aberrantly expressed in breast cancer cells, most notably in HER2-positive tumors. We propose to investigate how expression of LVA calcium channels may promote cancer cell growth and progression, and confer resistance to therapy. We will further investigate whether LVA channel inhibitors, mibefradil and similar drugs, can be employed to treat an advanced HER2-positive breast cancer. Our proposed research is expected to reveal an important mechanisms that support the progression of HER2 breast cancer.

Subject Categories:

  • Genetic Engineering and Molecular Biology
  • Inorganic Chemistry
  • Medicine and Medical Research

Distribution Statement:

[A, Approved For Public Release]