MATRIX METALLOPROTEINASE INHIBITION AS A NOVEL ANTICANCER STRATEGY - A REVIEW WITH SPECIAL FOCUS ON BATIMASTAT AND MARIMASTAT

Matrix metalloproteinases (MMPs) are a homologous family of enzymes th at are involved in tissue remodeling and morphogenesis. Collectively, these enzymes are capable of degrading all components of the extracell ular matrix, and they play an important role in normal physiologic con ditions, such as wound healing and other processes involving tissue re modeling. However, increased activity of these enzymes now has been ob served in a number of different pathological conditions, and it has be en hypothesized that such increased activity of MMPs might play a role in the pathogenesis of these conditions. Cancer is one such condition ; extracellular matrices constitute the principal barrier to tumor gro wth and spread, and there is growing experimental evidence that malign ant tumors utilize MMPs to overcome these barriers. Consequently, inhi bitors of MMPs represent an attractive target for a new class of antic ancer agents. Marimastat and batimastat are potent broad spectrum inhi bitors of all the major MMPs and have been shown to prevent or reduce spread and growth of a number of different malignant tumors in numerou s animal models. Both agents are now in advanced clinical testing in a number of different solid tumors in North America and Europe. The pur pose of this paper is to review available preclinical and emerging cli nical data, using batimastat and marimastat as prototype MMP inhibitor s in the cancer area. (C) 1997 Elsevier Science Inc.