Understanding the Epidemiology, Natural History, and Key Pathways Involved in Prostate Cancer

Age-adjusted incidence of prostate cancer among different racial/ethnic populations of men (2001-2005). Data from Ries et al.²

Different zones of prostate. Adapted with permission, from Greene et al.^15a © Elsevier.

Pathways involved in prostate cancer (PCa) growth and progression. (Left) Summary of biochemical pathways that are potential targets for PCa intervention and risk reduction. (Right) Androgen receptor (AR) and receptor tyrosine kinase signaling targeted by therapeutic agents to inhibit cell growth, deregulated cell cycle progression, and cell survival. Sideways T indicates areas in which intervening in cellular pathways of disease might be possible. Dashed rectangle outlines process by which 5α-reductase converts testosterone to dihydrotestosterone (DHT), which binds to ARs, leading to nuclear translocation and transcriptional activation of androgen-responsive genes. Potential interaction with other signaling pathways, such as ERK1/2, also displayed. 5αR, 5α-reductase; CDK, cyclin-dependent kinase; CDKI, cyclin-dependent kinase inhibitor; EGF, epidermal growth factor; EGFR, epidermal growth factor receptor; ERK1/2, extracellular signal-regulated kinase 1/2; HIF-1α, hypoxia-inducible factor-1 α-subunit; IGF-1, insulin-like growth factor 1; IGF-1R, insulin-like growth factor 1 receptor; IGFR, insulin-like growth factor receptor; LAP, leucine aminopeptidase; MMP, matrix metalloproteinase; NF-κB, nuclear factor kappa B; Rb-E2F, retinoblastoma; RTK, receptor tyrosine kinase; STAT, signal transducers and activators of transcription; TGFα, transforming growth factor α; TLR, toll-like receptors; uPA, urokinase plasminogen activator; VEGF, vascular endothelial growth factor. Adapted, with permission, from Singh and Agarwal.⁴² ©Society for Endocrinology.