Comprehensive Molecular Profiling of African-American Prostate Cancer to Inform on Prognosis and Disease Biology
Abstract
Objective and Rationale: Prostate cancer is more frequent, as well as more often lethal, in black/African American men compared to white/Caucasian men. Our team s work, supported by that of others, suggests that while socioeconomic factors contribute to these racial disparities, prostate cancer is still more aggressive in African American men when controlling for these factors. Recent technological advances have enabled extraordinary insight into alterations in gene expression patterns and acquired mutations that occur in prostate cancer. Unfortunately, for multiple reasons, the vast majority of our knowledge comes from studying overwhelmingly Caucasian populations. Importantly, novel technologies are now making these technological advances applicable to routine pathological specimens collected at diagnosis or surgery, which until recently could not be comprehensively studied. Likewise, these technologies have enabled the development of clinical assays that provide patients with estimates of the risk that their prostate cancer will behave aggressively. Although these tests are being used to guide clinical decision making and aggressively marketed, it is unclear if they are applicable to African American men and if they could be improved by including unique alterations that may only occur (or be more frequent) in prostate cancer arising in African American men. To address these issues, we have formed a collaborative team from investigators at two institutions and an industry partner, led by clinician scientists with expertise in prostate cancer molecular pathology and health disparities research. Our objective in this profile is to perform a comprehensive molecular assessment of a well-annotated prostate cancer in African American men. We will specifically evaluate the performance of currently available prognostic tests in African American men, as well as identify novel alterations that may explain the aggressive behavior of prostate cancer in these men. Lastly, we will determine whether incorporation of our comprehensive molecular assessment can improve the performance of these prognostic tests specifically in African American men. Importantly, our analyses will consider the anatomic location of the cancer in the prostate (anterior or posterior to the urethra), which our previous research shows varies between African American and Caucasian men. Lastly, we will be able to compare our results to previously studied cohorts of similar prostate cancer arising in Caucasian men. Applicability: Findings from our proposed research would have both immediate and long-term clinical and translational research applicability. First, through partnering with an industry partner and utilizing their currently available prognostic assay, we will evaluate the performance of this prognostic assay in African American patients with prostate cancer. In addition, through leveraging "extra" data generated as part of this assay, we can similarly evaluate other available prognostic assays. Additionally, our research will determine whether incorporating novel molecular data generated in this proposal, as well as anatomic tumor location, can improve the performance of currently available prognostic assays. This will ensure that African American men are making the most informed decision about individual prostate cancer management. Together, these results are critical to the over 35,000 African American men diagnosed with prostate cancer each year in the United States. Critically, the approaches used in this application to identify and validate novel molecular alterations are optimized for routine pathological specimens and can be directly translated to clinically useful tests once validated in additional cohorts. Given their different biological behavior, we expect to identify molecular alterations that differ in frequency between prostate cancers arising in African American and Caucasian men through our comprehensive approach. T
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 29, 2016
- Source ID
- W81XWH1510661
Entities
People
- Scott Tomlins
Organizations
- United States Army
- University of Michigan