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; Marie      Ranson

Abstract

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.

Keywords: Breast cancer, metastasis, adjuvant chemotherapy, plasminogen activation system, uPA, protease, uPAR, inhibitor, antagonist, WX-UK1