Matrix metalloproteinases as emerging targets in anticancer therapy: status and prospects

Abstract

A major hallmark of malignant disease is the capacity of cancer cells to cross tissue boundaries and spread to distant sites throughout the body. Extracellular matrix-degrading enzymes are thus required to break down structural barriers to invasion and metastasis. Extensive and compelling evidence indicates that several members of the matrix metalloproteinase (MMP) family of enzymes play a key role in this regard and forms the rationale for the development and testing of compounds that can inhibit their proteolytic activity. In addition, data now indicate that MMPs contribute to other aspects of cancer, including angiogenesis and the initial stages of tumour development, thus expanding the potential clinical utility of MMP inhibitors (MMPIs). Conversely, some MMPs may defy cancer progression and others may not participate in cancer, but undoubtedly play normal physiologic roles. These possibilities and the mechanisms underlying the influence of MMPs in cancer must be understood and considered in the design of therapeutic agents in order to optimise their efficacy and minimise their toxicity. Herein we review the biology and regulation of the MMPs, their roles in cancer development and progression, the status of preclinical and clinical efforts aimed at inhibiting their activity and the challenges and promise ahead.

• angiogenesis
• cancer
• clinical trials
• matrix metalloproteinases
• matrix metalloproteinase inhibitors
• preclinical trials