Matrix metalloproteinase inhibitors: past lessons and future prospects in breast cancer

The matrix metalloproteinases (MMPs) play a central role in invasion and me tastasis. However, despite striking activity in preclinical. models, the cl inical development of the matrix metalloproteinase inhibitors (MMPIs) has b een difficult. The results, of important phase III trials are now emerging and it is therefore opportune to review the current state of the MMPIs. In this article the evidence for the role of MMPs in the progression of breast cancer, the development of the MMPIs and the recent phase III results are discussed. Despite the problems encountered it is hoped that the MMPIs may yet provide another mechanism for the long-term control of micrometastatic disease. Furthermore, important lessons can be learnt from their developmen t that are relevant to. the development of other biological agents. (C) 200 1 Harcourt Publishers Ltd.