New Developments in the Pathobiology of Prostate Disease

Our understanding of the cellular and molecular basis of prostate disease has increased substantially in the last decade. This review discusses the most recent advances in five key areas: ontogeny of prostate cancer, differential gene expression in prostate cancer, biomarkers for prostate cancer and benign prostatic hyperplasia (BPH), role of the androgen receptor in prostate cancer, and 5α-reductase isoenzyme expression in prostate disease. Knowledge of the ontogeny of prostate cancer cells has led to a greater understanding of the molecular and cellular basis for the transition from normal epithelium to prostatic intraepithelial neoplasia and carcinoma. Our understanding of oxidative stress and inflammation suggests a role for antioxidative and anti-inflammatory agents in preventing or treating prostate cancer. The underlying androgen drive for prostate cell growth and differentiation also supports the role of inhibition of 5α-reductase to reduce the risk of progression to cancer. Significant evidence indicates that synthesis of dihydrotestosterone in prostate cancer is driven by types 1 and 2 5α-reductase. This suggests that a 5α-reductase inhibitor that inhibits both isoenzymes may have a role in preventing and/or treating prostate cancer; the former is being tested in the large-scale Reduction by Dutasteride of Prostate Cancer Events study. Work on biomarkers of prostate disease has advanced and several viable candidates exist for diagnosing prostate cancer and discerning those likely to recur or progress. These markers should have a significant impact on the diagnosis and staging of prostate cancer, delineate men with BPH or indolent prostate cancer, and reduce the need for invasive testing.