Molecular Pathogenesis of Prostate Cancer: Somatic, Epigenetic, and Genetic Alterations

Publisher Summary Prostate cancer is one of the most common malignancies in Western men, and risk factors include age, race, inherited genes, and environmental factors, such as diet. Although the precise molecular mechanisms underlying carcinogenesis and progression are currently unknown, histological studies indicate a multistage developmental progression. The existence of premalignant lesions has been demonstrated in the prostate based on shared histological and molecular features with adenocarcinoma, as well as prevalence and severity. Prostate cancer arises from the accumulation of genetic and epigenetic alterations. Cytogenetic analyses have demonstrated the prevalence of chromsomal aberrations associated with prostate tumorigenesis and many genes that map to deleted or amplified regions have been investigated for their roles in disease progression. In recent years, genome-wide profiling of prostate tumors has led to the identification of a number of biomarkers and pathways that are altered in prostate cancer, some of which may be potential molecular targets for therapy. Despite the advancing knowledge of genes altered in prostate adenocarcinoma, the precise molecular pathways, their combinatorial relation, and the ordering of events utilized in the development of preneoplastic lesions and adenocarcinoma are still being refined. To elucidate mechanisms and to begin to test new therapies and preventative strategies for human prostate cancer, a number of groups have been developing novel animal models of prostate cancer. These models will help to define many aspects of the molecular and cellular pathogenesis of prostate cancer, such as the role of inflammation, angiogenesis, and stromal-epithelial interactions. This chapter highlights the recent advances in the understanding of the molecular pathology of prostatic adenocarcinoma and the latest developments in mouse prostate cancer models.