Blocking the Metastatic Phenotype in Prostate Cancer Through Direct Inhibition of the ETV/PEA3 Transcription Factors
Abstract
The transition of localized prostate cancer to metastatic disease is a major contributor to increased disability and death associated with advanced disease. For this reason, one of the four Fiscal Year 2014 Prostate Cancer Research Program overarching challenges is to "Develop effective treatments and address mechanisms of resistance for men with high-risk or metastatic prostate cancer" and a Focus Area is "Therapy." This project directly addresses both the challenge of addressing and understanding metastatic disease with a focus of illuminating a new path to therapy for advanced prostate cancer. This will be accomplished by targeting a newly identified signature of prostate cancer metastases, the appearance of a protein called ETV4. This protein controls the cell s ability to invade tissues, an important feature of metastasis. It has been shown in a mouse model of metastatic prostate cancer that if this protein is removed, the formation of metastases is much diminished, and these and other studies indicate that a molecule that could block the ability of the protein to function could be a powerful therapy to prevent the formation of metastases. We will test this hypothesis by discovering drug-like molecules that inhibit the ability of ETV4 to turn on invasion programs in prostate cancer cells and directly test how these molecules affect key aspects of the metastatic process. In addition, we will test the molecules in combination with advanced drug candidates that target other parts of the metastatic pathway to identify the most effective strategy for eliminating metastatic potential. Once completed, this study will illuminate a new mechanism for targeting the metastatic process in prostate cancer and enable new therapeutic discovery specifically aimed at metastatic disease. Also important, however, is that these studies will provide new tools for the broader cancer biology community to understand the transformation of cancers from localized to metastatic.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510481
Entities
People
- Anna K. Mapp
Organizations
- United States Army
- University of Michigan