Prostate-specific antigen: an overlooked candidate for the targeted treatment and selective imaging of prostate cancer

摘要

The role of prostate-specific antigen (PSA) or kallkirein-related peptidase 3 (KLK3) as a biomarker for prostate cancer is well known; however, the precise physiologic role of its serine protease activity in prostate cancer remains a mystery. PSA is produced at high levels by both androgen-dependent and -independent prostate cancers. Studies have documented high levels of active PSA in the milieu surrounding osseous and soft tissue metastases. This evidence, coupled with growing experimental evidence, suggests that PSA plays an important role in the pathobiology of prostate cancer. These observations support the development of PSA-selective inhibitors as useful tools for the targeted treatment and imaging of prostate cancer. Here we review the research that has been conducted to date on developing selective inhibitors for PSA. The different approaches used to determine PSA substrate specificity and for creating inhibitors is discussed. In addition, the unique active site characteristics of PSA and how these motifs aided our research in developing PSA targeted agents is highlighted.