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 (PAI-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.