The urokinase plasminogen activator receptor as a gene therapy target for cancer

Urokinase plasminogen activator (uPA) and/or its receptor (uPAR) are essential for metastasis, and overexpression of these molecules is strongly correlated with poor prognosis in a variety of malignant tumours. Impairment of uPA and/or uPAR function, or inhibition of the expression of these components, impedes the metastatic potential of many tumours. Several approaches have been employed to target uPAR with the aim of disrupting its ligand-independent action or interaction with uPA, including the more recent antigene technology. This review discusses the in vivo use of antigene approaches for downregulating uPAR as a potential therapy for cancer. Preclinical studies are advancing towards the translational phase, provided that established orthotopic tumours, which mimic clinical progression and presentation, are treated using clinically acceptable modes of nucleic acid delivery.