The matrix metalloproteinases and their synthetic inhibitors in tumor progression

The matrix metalloproteinases (MMPs) form a family of more than 20 proteases which are collectively able to degrade the major components of the extracellular matrix They also have been described to have proteolytic activity for several non-matrix proteins. The activity of MMPs in the extracellular milieu is regulated by different mechanisms controlling their activation and by the presence of natural inhibitors designated tissue inhibitors of matrix metalloproteinases (TIMPs). Over the lost two decades, there has been a large number of publications suggesting that MMPs play an important role in tumor promotion, proliferation, invasion, metastasis and angiogenesis. MMPs are, therefore, a potential target in cancer therapy. Several synthetic MMP inhibitors have been developed and have shown anti-tumor activity in a variety of animal models of cancer. However, the recent clinical trials performed with these synthetic inhibitors in patients with advanced cancers have not always shown therapeutic efficacy. This article reviews the complex role of MMPs during tumor progression and discusses the benefits and limitations of synthetic MMP inhibitors in cancer therapy.