Disparities in Intratumoral Steroidogenesis.

摘要

Prostatic adenocarcinoma (PCa) is the most common form of non- cutaneous cancer and second most lethal cancer in American men but demonstrates tremendous disparity in both incidence and severity between African American men (AAM) and Caucasian men (CM). We have identified prostatic intratumoral steroidogenesis as a biological factor that may explain some or much of the disparity in lethal PCa rates between AAM and CM. We proposed testing this hypothesis by examining intratumoral steroidogenesis in the prostates of men following radical prostatectomy and in vivo model systems. In this project period we have finished our initial round of in vivo modeling and have demonstrated that hypercholesterolemia contributes to increased androgen levels and higher levels of nuclear localized AR as well as prostate tumor growth (as reported in last year s progress report) in our model mimicking the human patient situation in which androgen deprivation therapy (castration) is applied after tumor initiation. Blinded end point testing is ongoing and we anticipate further strengthening the statistical significance of our findings as we analyze more tumors. The final data are anticipated to reveal that, as hypothesized, hypercholesterolemia contributes to faster relapse after castration and increases intratumoral steroidogenesis.