Intratumoral Heterogeneity of Aggressive Molecular Biomarkers in Lethal Primary Prostate Cancer
Abstract
Although most patients with prostate cancer will be cured by surgery and/or radiation, a small group of patients will develop metastases and ultimately die of prostate cancer. If we could identify patients early who will eventually die of prostate cancer, it is possible that they could receive additional treatments that would save their lives. Over the past 15 years, our understanding of the biology of prostate cancer has increased dramatically, and a number of specific genetic changes (i.e., biomarkers) have been identified that help us predict which patients with die from prostate cancer. At the same time, however, other research has shown that these genetic changes can vary significantly within a single tumor (a concept known as intratumoral heterogeneity), and the possibility of intratumoral biomarker heterogeneity represents a significant challenge to our ability to predict which patients will die from prostate cancer. In this study, we hypothesize that tumors in patients who eventually die from prostate cancer show increased intratumoral biomarker heterogeneity that is associated with other types of genetic changes. To examine this hypothesis, we will assess how frequently specific biomarkers show intratumoral heterogeneity in these tumors and identify the types of corresponding genetic changes. The results of this proposed research will have important implications for patients with early prostate cancer that is treated by surgery and/or radiation, as our findings will help improve the ability of laboratory tests to predict which of these patients will die of prostate cancer. Thus, this proposed research has the potential to enhance the well-being of Service members, Veterans, and other men with prostate cancer by improving early identification of and nominating potential treatments for those who will die from their disease (FY18 PCRP Overarching Challenge). There are no specific risks associated with this proposed research, and the potential benefits to prostate cancer patients could be available within 5 years. Aaron M. Udager, M.D., Ph.D., (Principal Investigator) is an Assistant Professor of Pathology at the University of Michigan Medical School (UMMS). Dr. Udager is a pathologist with expertise in prostate cancer. He is focused on applying cutting-edge approaches to address important clinical and translational questions in prostate cancer research. Arul M. Chinnaiyan, M.D., Ph.D., (Designated Mentor) is the S.P. Hicks Endowed Professor of Pathology and Urology at UMMS. He is an internationally recognized expert in cancer research and directs a large research laboratory that focuses on eliminating death due to prostate cancer. Under the guidance of Dr. Chinnaiyan and within the larger prostate cancer research community at the University of Michigan, Dr. Udager will hone the skills necessary to successfully complete the proposed research, and this award will provide Dr. Udager with the needed funding support to establish himself as an independent physician-scientist with a research focus on prostate cancer. In addition to the potential benefits to patients, the results of this proposed research will also help scientists better understand the types of genetics changes that occur in tumors from patients who eventually die from prostate cancer. This is an important first step in developing new ways to treat these aggressive tumors, with the ultimate goal of reducing and/or eliminating death from prostate cancer (FY18 PCRP Overarching Challenge).
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910407
Entities
People
- Aaron Udager
Organizations
- United States Army
- University of Michigan