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 that are involved in tissue remodeling and morphogenesis. Collectively, these enzymes are capable of degrading all components of the extracellular matrix, and they play an important role in normal physiologic conditions, such as wound healing and other processes involving tissue remodeling. However, increased activity of these enzymes now has been observed in a number of different pathological conditions, and it has been 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 growth and spread, and there is growing experimental evidence that malignant tumors utilize MMPs to overcome these barriers. Consequently, inhibitors of MMPs represent an attractive target for a new class of anticancer agents. Marimastat and batimastat are potent broad-spectrum inhibitors of all major MMPs and have been shown to prevent or reduce spread and growth of a number of different malignant tumors in numerous animal models. Both agents are now in advanced clinical testing in a number of different solid tumors in North America and Europe. The purpose of this paper is to review available preclinical and emerging clinical data, using batimastat and marimastat as prototype MMP inhibitors in the cancer area.
Rasmussen
H S
HS
British Biotech Inc., Annapolis, MD 21401, USA.
McCann
P P
PP
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy; D015179:Colorectal Neoplasms / Q000188:drug therapy; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D006391:Hemangioma / Q000188:drug therapy; D006801:Humans; D006877:Hydroxamic Acids; D008545:Melanoma / Q000188:drug therapy; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D051379:Mice; D010051:Ovarian Neoplasms / Q000188:drug therapy; D010190:Pancreatic Neoplasms / Q000188:drug therapy; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000188:drug therapy; D013876:Thiophenes / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D011480:Protease Inhibitors; D013876:Thiophenes; D010649:Phenylalanine; C080985:batimastat; C100342:marimastat; D008666:Metalloendopeptidases