Proteolysis of extracellular matrix (ECM) and basement membrane is an essential mechanism used by
cancer cells for their invasion and
metastasis. The ECM
proteinases are divided into three groups:
metalloproteinases,
cysteine proteinases and
serine proteinases. The
urokinase plasminogen activator (uPA) system is one of the
serine proteinase systems involved in ECM degradation. Members of this system, including uPA and its
receptor (uPAR), are overexpressed in several malignant
tumors. This system plays a major role in adhesion, migration, invasion and
metastasis of
cancer cells, thus making it an important target for anticancer
drug therapy. Several strategies, including the use of antisense
oligodeoxynucleotides,
ribozymes,
DNAzyme, RNAi, uPA inhibitors, soluble uPAR, catalytically inactive uPA fragments, synthetic
peptides and synthetic hybrids are under study, as they interfere with the expression and/or activity of uPA or uPAR in
tumor cells. Herein, we discuss the various
pharmaceutical strategies under investigation to combat the uPA activity in
cancer.