The role of the urokinase-type plasminogen activator (uPA) and its inhibitor (PAI-1) in breast cancer

Abstract

Background: This paper describes the role of urokinase-type plasminogen activator (uPA) and its inhibitor, PAI-1, in breast cancer invasion and metastasis. These two parts of fibrinolytic system were the first novel tumor biological factors to be validated at the highest level of evidence (LOE I) regarding their clinical utility in breast cancer. Conclusions: Numerous independent studies have demonstrated that breast cancer patients with low levels of uPA and PAI-1 in their primary tumor tissue have a significantly better survival than patients with high levels of either factor. uPA and PAI-1 are recognized as level 1 tumor prognostic markers in early breast cancer. The methodology of determination is standardized and validated. The involvement of uPA and PAI-1 in cancer progression identifies its components as suitable targets for anti-cancer therapy. Several therapeutic approaches have been shown to be active in vitro, and are being currently tested in phase 2 clinical trials. The information provided in this brief review aims to inform the professional public of the latest knowledge and to promote greater interest in the role of the plasminogen activator system in breast cancer.