Prostate cancer is comprised of 4 "zones". 1) peripheral, which is the site of roughly 80% of prostate cancers. 2) transition, which is the site of nearly 10% of prostate cancers. 3) central, which is the site of 5% of prostate cancers. 4) anterior fibromuscular, which is the location of 5% of prostate cancers. Key molecular alterations in prostate-cancer cells as critical determinants of the phenotype of prostate cancer cells: Carcinogen defences (GSTP1), Glutathione S-transferases (GSTP1) are detoxifying enzymes, cells of prostatic intraepithelial neoplasia are devoid of GSTP1. Growth-factor-signalling pathways (NKX3.1, PTEN, and p27) - regulate growth and survival of normal prostate cells. Inadequate levels of PTEN and NKX3.1 lead to a reduction in p27 levels and to increased proliferation and decreased apoptosis. Androgens (AR) • Transcription factor that is normally activated by its androgen ligand • If the altered activity of AR co-activators → emergence of androgen-independent prostate cancer.