Targeting urokinase-type plasminogen activator and its receptor for cancer therapy

Cancer invasion and metastasis are highly complex processes and a serine protease urokinase-type plasminogen activator/urokinase-type plasminogen activator receptor system has been postulated to play a central role in the mediation of cancer progression. Of note, malignant tumor urokinase-type plasminogen activator and urokinase-type plasminogen activator receptor levels have been found to vary considerably, and to be related to patient prognosis. In mouse models, the urokinase-type plasminogen activator/urokinase-type plasminogen activator receptor system has been studied extensively as a target for anticancer therapy using a variety of approaches. In this review, we discuss the advances in the various modalities that have been used to target the urokinase-type plasminogen activator/urokinase-type plasminogen activator receptor system, including protein-based and peptide-based drugs, antisense therapy, and RNA interference technology. In particular, preclinical mouse model studies that used human tumor xenografts; are reviewed. Anti-Cancer Drugs 17:1109-1117 (c) 2006 Lippincott Williams & Wilkins.