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Targeting Tumor-Initiating Cells for the Therapeutics of Breast Cancer

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[Technical Report, Annual Report]

Corporate Author:

The University of Iowa

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HER2 breast cancers are a highly aggressive form that occurs in 20-30 of metastatic breast cancers and correlates with poor prognosis. HER2 breast cancers are usually treated with HER2-targeted therapy, but cancers quickly develop resistance to the therapy within 1 to 2 years. The mechanisms underlying resistance remain largely unknown but are attributed to a reservoir of stem-cell-like, tumor-initiating cells TICs. Under the pressure of current therapies, these cells have a survival advantage and may escape therapies, and so likely account for drug resistance, tumor recurrence, and metastasis. This proposal aims to determine the role of Gio-coupled receptors Gio-GPCR signaling in regulating the tumorigenicity of TICs to drive HER2 breast cancer growth and metastasis, and confer drug resistance to the HER2-targeted therapy. Our studies thus far have demonstrated that Gio-GPCR signaling is essential for the initiation and progression of HER2-induced mammary tumors in mice, and HER2-mediated human breast cancer cell growth and migration in vitro. Moreover, we provided the evidence that Gio-GPCRs drive tumor progression at least in part through enhancing the tumorigenicity of TICs. The proposal was terminated early because of partial overlapping with a NCI-funded R01 proposal. Nevertheless, findings from these studies have laid the foundation for further investigation of the function and mechanisms of Gio-GPCRs in driving HER2 breast cancer.

Subject Categories:

  • Medicine and Medical Research
  • Biochemistry

Distribution Statement:

[A, Approved For Public Release]