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 biochemical differences exist between prostate cancers of African American and European American 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 preliminary studies, we have profiled the metabolome of prostate cancers from African-American and European American men and have identified specific racially distinct metabololites as well as biological pathways associated with each. In this proposal, we will i) validate and refine the metabolomic profile of prostate cancers from African American and European American men, ii) evaluate the role of specific biochemical pathways in prostate cancers of African American and European American men and iii) develop urine based metabolic markers for high risk prostate cancer in African American and European American men. At the conclusion of this study, we will have developed a racially derived metabolomic model for prostate cancer as well as identified candidate pathways for future drug targeting.
At present, it is not known how the prostate cancer metabolome contributes to health disparities. The information gleaned from this proposal could rapidly revolutionize current diagnostic, prognostic and therapeutic approaches by revealing the biological underpinnings of prostate cancer health disparity.
|Putluri, Nagireddy; Maity, Suman; Kommagani, Ramakrishna et al. (2014) Pathway-centric integrative analysis identifies RRM2 as a prognostic marker in breast cancer associated with poor survival and tamoxifen resistance. Neoplasia 16:390-402|
|Kaushik, Akash K; Vareed, Shaiju K; Basu, Sumanta et al. (2014) Metabolomic profiling identifies biochemical pathways associated with castration-resistant prostate cancer. J Proteome Res 13:1088-100|
|Terunuma, Atsushi; Putluri, Nagireddy; Mishra, Prachi et al. (2014) MYC-driven accumulation of 2-hydroxyglutarate is associated with breast cancer prognosis. J Clin Invest 124:398-412|
|Khan, Amjad P; Rajendiran, Thekkelnaycke M; Ateeq, Bushra et al. (2013) The role of sarcosine metabolism in prostate cancer progression. Neoplasia 15:491-501|