Therapeutic potential of siRNA-mediated targeting of urokinase plasminogen activator, its receptor, and matrix metalloproteinases.

Targeting proteases and their activators would retard the invasive ability of cancer cells, and has been shown to induce apoptosis in certain instances. Various methods have been developed to specifically target protease molecules in an attempt to retard invasion and migration. Of these methods, RNA interference (RNAi) holds great therapeutic potential. RNAi technology is now being used to target specific molecules for use as potential anti-cancer agents. RNAi-mediated silencing is almost catalytic when compared to anti-sense silencing. Of these targets, the uPAR-uPA system and MMPs holds great promise. Targeting uPA/uPAR may provide additive or synergistic treatment benefits if used in combination with conventional therapeutics such as chemotherapy or radiation. Studies point to the fact that specifically targeting MMP-9 or MMP-2 singly or in combination with other proteases could have specific therapeutic implications in the treatment of cancer. In this chapter we discuss the therapeutic potential of siRNA-mediated targeting of the uPAR-uPA system and MMPs as therapeutic agents for the treatment of cancer.