A third group of angiogenesis inhibitors are directed against one of the initial products made by growing endothelial cells, namely, the MMPs, enzymes that catalyze the breakdown of the extracellular matrix. Because breakdown of the matrix is required before endothelial cells can migrate into surrounding tissues and proliferate into new blood vessels, drugs that target MMPs also can inhibit angiogenesis.

Several synthetic and naturally occurring molecules that inhibit the activity of MMPs are currently being tested to see if interfering with this stage in the process of angiogenesis will prolong the survival of cancer patients.