Peptides and Small Molecules Targeting the Plasminogen Activation System: Towards Prophylactic Anti-Metastasis Drugs for Breast Cancer
Joel D. A. Tyndall, Michael J. Kelso, Phillip Clingan and Marie Ranson
Affiliation: National School of Pharmacy,University of Otago, PO Box 913, Dunedin, 9054, New Zealand.
Keywords: Breast cancer, metastasis, adjuvant chemotherapy, plasminogen activation system, uPA, protease, uPAR, inhibitor, antagonist, WX-UK1
Breast cancer is the most common malignancy afflicting Western women today and is responsible for many deaths due to metastatic disease. Upregulation of the plasminogen-activation system (PAS) has been shown to correlate with poor prognosis in metastatic breast cancer and targeting this system represents an attractive strategy for the development of anti-metastasis prophylactic drugs. Two promising classes of PAS-targeting agents are inhibitors of the serine protease activity of urokinase plasminogen activator (uPA) and antagonists of the interaction of uPA with its cell surface receptor (uPAR). This review begins with a brief overview of the role of PAS in cancer metastasis before describing in detail a subset of the small molecules and peptides from the patent literature that target either uPA activity or uPA/uPAR interactions for use as anti-metastasis drugs.
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