KLK3

KLK3 (kallikrein-related peptidase 3), commonly termed prostate-specific antigen (PSA), is a serine protease encoded by the KLK3 gene. Also known as P-30 antigen or γ-seminoprotein, PSA enzymatically cleaves semenogelin in seminal fluid to liquefy semen, facilitating sperm motility. Its expression is tightly regulated by androgen receptor (AR)-mediated signaling, linking it to prostate development and pathology. Elevated PSA levels in serum are a hallmark of prostate cancer, serving as a diagnostic biomarker, though benign conditions like prostatic hyperplasia or inflammation may also elevate PSA. While PSA screening remains controversial due to false positives, therapeutic strategies targeting PSA are under exploration. These include PSA-activated prodrugs (e.g., L-377,202) and immunotherapies like PROSTVAC-VF, which leverages PSA as an antigen. Recent advances also focus on PSA-directed antibody-drug conjugates (e.g., EC-17) and inhibitors blocking its proteolytic activity to mitigate cancer progression. However, specificity challenges persist in distinguishing malignant from benign PSA elevation.