New concepts in the pathology of prostatic epithelial carcinogenesis

The development of drugs to prevent prostate cancer is underway, yet monito ring the potential efficacy of these agents during clinical trials relies o n measuring intermediate endpoints. In this review, various candidate marke rs are presented that are under different stages of evaluation as intermedi ate endpoint biomarkers. In addition, the near future will bring an unprece dented wave of new potential biomarkers. For instance, through genomics-bas ed methods many new genes are being discovered whose altered expression may be involved ill different phases of prostate cancer development and progre ssion. In the development of rational approaches for selecting which of the se untested biomarkers may be useful to measure systematically, there must be an improved understanding of the mechanisms of prostatic carcinogenesis. We submit that this improved understanding will come through new knowledge of the biology of normal prostate epithelial cells, the determination of t he precise target cells of transformation, and how their growth regulation is genetically and epigenetically perturbed during the phases of initiation and progression. In this review, therefore, we also present our recent imm une-mediated oxidant injury and regeneration hypothesis of why and how the prostate is targeted for carcinogenesis. (C) 2001, Elsevier Science inc.