Scientific Objective/Rationale: The long-term objective of our research plan is to reduce the disproportionate effects of prostate cancer on African-American men. A guiding principle of our methodology is that biochemical differences exist between prostate cancers of African American and Caucasian origin and that these differences can explain, in part, prostate cancer health disparity. In this application, we propose to use the technique of metabolomic profiling to uncover these underlying differences. Metabolomics describes the science of quantifying the levels of metabolites (e.g., small molecules) that are the byproducts of cellular metabolism. That is to say, in this kind of analysis we are measuring the biochemical entities (or metabolites) that are produced by the functional machinery of the cell. With knowledge of the identity of specific metabolites, we can infer the biological processes that produced them, thus gaining insight into a cell's metabolism. To date, a metabolomic analysis of prostate cancer health disparity has not been reported. In this project, we will use state-of-the-art technology to determine the metabolomic profile of prostate cancers from African-American and Caucasian men with an eye towards ascertaining the profiles of indolent and aggressive disease in a racially exclusive manner. At the conclusion of this study, we will have developed a metabolomically based, racially derived, prostate cancer prognostic model as well as identified candidate pathways for future drug targeting.

Applicability: The output from the proposed research has potential to help both African-American and Caucasian men with prostate cancer. Both populations may be helped by the use of metabolomically based prognostic models. Identifying men with aggressive prostate cancer will allow the proper allocation of additional therapy to those who need it the most. In addition, the results from this study will serve as a springboard for future studies that seek to target relevant biologically active pathways in aggressive prostate cancer. There are no inherent direct risks to individuals from this research proposal. We expect that pending external validation of our findings by other groups, the clinical utility of our proposal may be realized within 5 years of the completion of the stated research aims. The latter will include development of a non-invasive predictive panel of metabolomic markers in urine for high-risk prostate cancer in African-American men.

Overall, the likely contributions of this study to advancing research are (i) establishing the metabolomic profile of high-risk prostate cancer in African-American and European-American men that could be used in the long term to develop racially distinct markers for early detection high-risk prostate cancer (in urine) and (ii) documenting the prognostic and potential biological implications of specific metabolites/biochemical processes in a racially exclusive manner. Such findings hold promise for reducing prostate cancer health disparity and benefitting all men with prostate cancer.