The urokinase plasminogen activator system: a rich source of tumour markers for the individualised management of patients with cancer

The urokinase plasminogen activator (uPA) system consists of the serine protease uPA, the glycolipid-anchored receptor, uPAR, and the 2 serpin inhibitors, plasminogen activator inhibitor-1 (PAl-1) and plasminogen activator inhibitor-2 (PAI-2). Recent findings suggest that uPA, uPAR and PAI-1 play a critical role in cancer invasion and metastasis. Consistent with their role in cancer dissemination, high levels of uPA, PAI-1 and uPAR in multiple cancer types correlate with adverse patient outcome. The prognostic value of uPA/PAI-1 in axillary node-negative breast cancer patients was recently validated using both a prospective randomised trial and a pooled analysis. Assay of uPA and PAI-1 may thus help identify low-risk node-negative patients for whom adjuvant chemotherapy is unnecessary. Finally, emerging data suggest that high levels of uPA and PAI-1 in breast cancer are associated with a preferential response to adjuvant chemotherapy but relative resistance to hormone therapy. The measurement of uPA components, especially in breast cancer, thus has the potential to help with individualised patient management. (C) 2004 The Canadian Society of Clinical Chemists. All rights reserved.