The introduction of testing for
prostate-specific antigen (PSA), a member of the fifteen-gene family of
kallikrein-related
peptidases and also known as
kallikrein-related
peptidase 3 (KLK3), in blood has revolutionized both the detection and management of
prostate cancer. Given the similarities between PSA and other KLK gene family members along with limitations of PSA as a
biomarker for
prostate cancer mainly in reference to diagnostic specificity, the potential roles of other members of this gene family as well as PSA derivatives and
isoforms in the management of
prostate cancer have been studied extensively. Of these, approaches to measure distinct molecular forms of PSA (free, intact, complexed PSA, and pro-PSA) combined with
kallikrein-related
peptidase 2 (KLK2), also known as hK2, have been considered holding particular promise in enhancing the diagnosis of
prostate cancer. Recently, an integrated approach of applying a panel of four
kallikrein markers has been demonstrated to enhance accuracy in predicting the risk of
prostate cancer at biopsy. This review presents an overview of
kallikreins, starting with the past and current status of PSA, summarizing published data on the evaluations of various KLKs as
biomarkers in the diagnosis, prognostication, and monitoring of
prostate cancer.