Investigating Genomic and Immunologic Features of Prostate Cancer in African American Men
Abstract
African American men with prostate cancer have lower survival rates compared to men from other racial/ethnic groups. While some factors, such as socioeconomic status and access to healthcare, play a role, differences in biological processes that influence cancer development and progression may also contribute to this disparity. For example, mutations will cause prostate cells to start growing abnormally. These cells will also need to escape or block the immune system in order to grow into an invasive tumor. Current therapies seek to block the male hormone upon which prostate cancer cells depend (hormone therapy/androgen deprivation therapy) or activate immune cells (immunotherapy) to attack the prostate cancer cells. However, molecular differences between African American men and other racial/ethnic groups that cause tumors to stop responding to therapy or make tumors more aggressive are not fully understood. In addition, African American men are underrepresented in prostate cancer DNA sequencing studies. In this proposal, we will use two novel technologies to identify molecular changes that contribute to resistance to therapy or disease aggressiveness in African American men with prostate cancer. In prostate cancer patients with metastatic disease, prostate tumor cells release DNA into the blood. We will collect and sequence this tumor DNA in the blood, called circulating tumor DNA. As prostate cancers stop responding to therapy, they can change their DNA to escape the actions of drugs. We will use genetic sequencing on the circulating tumor DNA of patients who have stopped responding to the drugs that decrease androgens to identify mutations that may be causing tumors to stop responding to therapy. These mutations will be compared to mutations found in prostate tumors and circulating tumor DNA of European American men to identify and compare tumor genetic changes that are similar or different. Prostate cancer cells grow in an environment with other cells, including immune cells. How prostate cancers escape the immune system is unknown, and turning on the immune system against prostate cancer has not yet been as successful as hoped. We will use a technology called single-cell RNA sequencing to identify different cancer and immune cells in prostate cancer biopsies. We will determine whether differences in these cell populations between African American and European American men contribute to more aggressive prostate cancers. All of these studies will use patient specimens collected at Boston Medical Center, which is an urban hospital that primarily serves underrepresented populations in the greater Boston area. Overall, these studies will uncover novel molecular features in African American prostate cancer and set the foundation for improved precision medicine in this population.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810489
Entities
People
- Franklin Huang
Organizations
- United States Army
- University of California, San Francisco