Journal
JOURNAL OF CLINICAL ONCOLOGY
Volume 21, Issue 2, Pages 383-391Publisher
AMER SOC CLINICAL ONCOLOGY
DOI: 10.1200/JCO.2003.02.083
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Funding
- NCI NIH HHS [R21CA89611, P01CA89021, K23-CA85436] Funding Source: Medline
- NIAID NIH HHS [R01AI42955] Funding Source: Medline
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Prostate-specific antigen (PSA) is an androgen-regulated serine protease produced by both prostate epithelial cells and prostate cancer (PCa) and is the most commonly used serum marker for cancer. It is a member of the tissue kallikrein family, some of the members of which are also prostate specific. PSA is a major protein in semen, where its function is to cleave semenogelins in the seminal coagulum. PSA is secreted into prostatic ducts as an inactive 244-amino acid proenzyme (proPSA) that is activated by cleavage of seven N-terminal amino acids. PSA that enters the circulation intact is rapidly bound by protease inhibitors, primarily alpha 1-antichymotrypsin, although a fraction is inactivated in the lumen by proteolysis and circulates as free PSA. This proteolytic inactivation, as well as the cleavage of proPSA to PSA, is less efficient in PCa. Serum total PSA levels are increased in PCa, and PSA screening has dramatically altered PCa presentation and management. Unfortunately, although high PSA levels are predictive of advanced PCa, a large fraction of organ-confined cancers present with much lower total PSA values that overlap those levels found in men without PCa. Measurement of free versus total PSA can increase specificity for PCa, and tests under development to measure forms of proPSA may further enhance the ability to detect early-stage PCa. PSA is also widely used to monitor responses to therapy and is under investigation as a therapeutic target. Finally, recent data indicate that there may be additional roles for PSA in the pathogenesis of PCa. (C) 2003 by American Society of Clinical Oncology.
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