Genetic and Epigenetic Vulnerabilities in Prostate Cancer of African American Men
Abstract
African American (AA) men are more likely to be diagnosed and die with high aggressive prostate cancer at a younger age compared to European American (EA) men. Common prostate cancer-associated genetic abnormalities are not found in a majority of prostate tumors from AA men. Thus far, studies that have comprehensively characterized prostate tumors in terms of genetics and epigenetics have been mostly derived from EA men. Therefore novel therapies, biomarkers, and risk stratification that have evolved from these studies generally would apply to EA men. A classic example is the FDA-approved prostate cancer-specific urine test that detects TMPRSS2-ERG RNA biomarkers in urine. Since AA men have significantly lower frequency of TMPRSS2-ERG fusion, this test may worsen prostate cancer health disparities. Growing evidence suggests that alternate tumor-promoting mechanisms that do not change the genetic code but still change gene expression, termed as epigenetics, are more commonly found in prostate tumors from AA men. One such epigenetic change is addition of methyl groups to specific locations in DNA referred to as DNA methylation. Different patterns of DNA methylation at certain gene locations have been found in prostate tumors from AA men compared to EA men. Still, the underlying molecular pathways driven by DNA methylation are unknown. Here we propose that unique molecular pathways driven by DNA methylation alterations influence prostate cancer biology in AA men. The identification these pathways will allow us to categorize prostate tumors from AA men with similar molecular features into different groups. The ability to use specific molecular characteristics in conjunction with clinical features will enable precise risk stratification of patients and identify lethal disease in AA men. These molecular features can be further used for developing alternative therapies and biomarker discovery for AA patients. Our specific aims are designed to address two main FY20 PCRP Overarching Challenges: defining the biology of lethal prostate cancer and developing tools to improve outcome of lethal prostate cancer in AA patients. We believe that, based on our discoveries in the current proposal, new molecular diagnostic and prognostic tests designed for AA patients could be developed within a matter of a few short years.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110462
Entities
People
- Anna Woloszynska-read
Organizations
- United States Army