Protease inhibitors in the control of tumor spread and angiogenesis

摘要

Tumor progression is associated with proteolytic degradation of the extracellular matrix, a critical step during angiogenesis, tumor invasion and metastasis formation. Among the enzymes that contribute to matrix degradation, the matrix metalloproteinases (MMPs) are thought to play a crucial role. MMPs are a family of zinc-dependent proteases, which degrade extracellular matrix components in physiological conditions. Increased MMP activity is associated with the malignant behavior of different tumor types. Inhibitors of MMPs, have been shown to control tumor growth and metastasis in experimental tumor models. Several natural and synthetic inhibitors of MMPs have been developed, and some of them, currently in clinical trials, will be presented. They prevent tumor growth, metastasis formation and angiogenesis, by acting both on tumor and endothelial cells. Preclinical studies suggest the use of MMP inhibitors in adjuvant settings and in combination with cytotoxic drugs.