Targeting Tumor-Initiating Cells for the Therapeutics of Breast Cancer
Abstract
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 Gi/o-coupled receptors (Gi/o-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 Gi/o-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 Gi/o-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 Gi/o-GPCRs in driving HER2 breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2017
- Accession Number
- AD1050362
Entities
People
- Songhai Chen
Organizations
- University of Iowa