Urokinase receptor antagonists: novel agents for the treatment of cancer

The interaction between the urokinase receptor (uPAR) and its ligand urokinase (uPA) mediates phenomena such as tissue remodelling, chemotaxis, tumour invasion, dissemination, proliferation, and angiogenesis. The broad-spectrum of biological processes that the uPA/uPAR interaction plays a role in has led researchers to speculate that this interaction may be a useful molecular target for therapeutic intervention in several pathological conditions, particularly in the prevention and inhibition of the dissemination of cancer cells. In syngeneic and xenograft murine tumour models, in which metastasis is driven by the uPA/uPAR interaction, inhibition of primary tumour growth, metastasis and angiogenesis has been shown with several proteins acting as uPAR antagonists. Immunohistochemistry, in conjunction with prognostic studies, has implicated the uPA/uPAR interaction in the dissemination of tumours, such as malignant melanoma, colon cancer, non-small cell lung cancer (NSCLC) and stomach cancer, as well as brea...