MMPs

Abstract

Matrix metalloproteinases (MMPs) are a family of endopeptidases that have long been associated with tumor invasion and metastasis. Several small molecule inhibitors were developed in the 1980s and 1990s, but all failed in large-scale clinical trials. While these failures undoubtedly dampened enthusiasm for further consideration of MMPs as important targets in cancer, continuing research has uncovered multiple roles for these proteases in many cancers as well as other diseases. Lessons learned from the early clinical failures have informed development of more specific reagents such as antibodies targeted to particular family members. Additionally, the strong association between MMP activity and tumor progression has stirred interest in the development of MMP-activated imaging agents that may be particularly useful for assessing response to other types of cancer therapy. Tumor-associated MMP activity has also been harnessed as a methodology for localized activation of pro-drugs, with the intention of reducing the toxic side effects of systemic chemotherapy. Overall, although broad-spectrum inhibition of MMPs is a failed clinical approach, there are still many potentially beneficial uses of targeting MMP activity in the cancer setting.