Targeting miR551b to Prevent Tumor Formation and Metastasis of Triple-Negative Breast Cancer
Abstract
This proposal will address the overarching challenges of “Eliminate the mortality associated with metastatic breast cancer” and “Identify what drives breast cancer growth; determine how to stop it.” The proposed work will expand upon our previous and novel findings regarding the composition of a recently identified microRNA amplified and overexpressed in triple-negative breast cancers (TNBCs). Using a combination of animal models, functional and bioinformatics as well as computational analysis, we will determine the effect of ant-sense small RNAs inhibit oncogenic miRNA to prevent the tumor formation and metastasis of TNBCs. Breast cancer is the leading malignancy among women. It is estimated in the United States that 255,180 new cases and 41,070 deaths occurred in the year of 2017 (American Cancer Society, Cancer Facts & Figures 2017). Approximately 20% of breast cancers are classified as TNBCs as they do not express estrogen receptors (ER), progesterone receptors (PR), and HER2 receptors. Specific risk factors that correlate with TNBC include reproductive factors (pregnancy and multiple childbirth) and obesity (lack of physical activity). In TNBC patients, the 5-year survival rate is much lower than other forms of breast cancer. Unfortunately, TNBCs are known to be more aggressive and metastatic with poor prognosis, while other types have better prognosis and outcome. Therefore, new approaches are needed to improve the clinical outcome for these patients. Our recent investments in understanding the molecular markers and drivers of TNBCs have yielded a deeper understanding of the mechanisms that promote tumor development and metastasis. Based on these studies, we identified a novel oncogene (miRNA-551b) highly amplified and overexpressed approximately in 30% of breast cancer patients, primarily in TNBCs. Importantly, our unpublished results identified that microRNA-551b act as a central mediator activates the pathways promote growth and metastasis of TNBC cells. Based on our preliminary data in cell culture model and three-dimensional (3D) culture model, we are proposing to use a novel class molecule known as anti-microRNAs (also known as anti-miR or antagomiR) to inhibit the levels of oncogenic microRNA-551b. We are expecting that the delivery of anti-microRNA-551b will prevent tumor formation and metastasis of TNBC. TNBC is highly aggressive, and there is no targeted therapy available for TNBC treatment. The majority of TNBC patients show metastasis to brain, lungs, and bone, which causes an extremely high rate of mortality. Therefore, we are expecting that our studies will provide novel approaches to prevent breast cancer initiation, growth, as well as metastasis, which will improve the quality of life of breast cancer patients.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810024
Entities
People
- Pradeep Chaluvally-raghavan
Organizations
- Medical College of Wisconsin
- United States Army