Targeting TMPRSS2-ERG Binding Partners in Prostate Cancer
Abstract
Scientific Objective and Rationale: The objective of my proposed research is to identify novel binding partners to ERG in prostate cancer in order to elucidate a mechanism and identify potential drug targets in TMPRSS2-ERG mediated disease. It was recently discovered that over 50% of all cases of prostate cancer harbor the TMPRSS2-ERG gene fusion, leading to overexpression of the ERG transcription factor. Despite this discovery, how TMPRSS2-ERG promotes cancer is still unknown; moreover, transcription factors have been difficult to target with drugs as they lack an active site and function primarily through protein-protein interactions. In my proposed research, I will use a combination of proteomic and genetic arrays to identify ERG binding proteins that alter the ERG gene signature. Many of our early hits incorporate members of the SWI/SNF chromatin remodeling family. Using this knowledge, I will determine a mechanism of ERG mediated oncogenesis in the prostate, which will facilitate the identification of novel drug targets; additionally, these studies could lead to identification of novel biomarkers that can detect early stages of prostate cancer. Career Goals: The goal of my research is to advance our basic understanding of prostate cancer development and to translate my research discoveries into the clinic. I foresee myself as an independent researcher at an academic institution working on prostate cancer development once I finish my postdoctoral studies. The research I proposed will use both genetic and proteomic approaches to investigate TMPRSS2-ERG mediated cancer, which affects nearly 50% of all prostate cancer patients. Successful completion of this research project will provide me essential scientific techniques for my subsequent independent researches in prostate cancer field. Moreover, the research proposal is only one part of my postdoctoral training program. Other components will include presenting to other research groups and at conferences, collaboration efforts with other prostate cancer groups, and publishing my findings. Moreover, Dr. William Hahn, a world-renowned scientist with expertise in prostate cancer, will mentor me at each stage of my training. Overall, the project outlined in this proposal will provide me with the necessary skills to achieve my career goals. Applicability of the Research: The research I proposed will potentially allow for therapeutics for patients with TMPRSS2-ERG mediated prostate cancer. As I mentioned, nearly 50% of all prostate cancer patients have the TMPRSS2-ERG translocation and this event is thought to take place early in prostate oncogenesis. Thus, if a therapeutic can be made to target this translocation, it may be used to treat prostate cancer or in a preventive role if the translocation is detected, but prostate cancer hasn t developed. Uncovering novel ERG binding partners will allow us to elucidate a potential mechanism by which TMPRSS2-ERG causes prostate tumorigenesis; moreover, binding partners that augment the ERG gene signature are prime candidates for drug targeting. Contributions to Advancing Prostate Cancer Research: The proposed research will contribute to the understanding of TMPRSS2-ERG mediated tumorigenesis. Additionally, this research will identify many novel proteins that can potentially play a role in prostate cancer. This will allow for the discovery of new drug targets; furthermore, elucidating a mechanism will allow for pinpointed targeted therapies and new potential biomarkers.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510659
Entities
People
- Gabriel Sandoval
Organizations
- Dana–Farber Cancer Institute
- United States Army