Matrix metalloproteinases: a dual role in breast cancer?

Abstract

353 ISSN 1758-1923 10.2217/BMT.13.36 © 2013 Future Medicine Ltd Breast Cancer Manage. (2013) 2(5), 353–356 Matrix metalloproteinases as cancer targets Breast cancer 5-year survival rates in the UK have improved up to 85% over the last decade due to earlier detection, better diagnosis and an increasing range of treatment options. Today, the majority of breast cancer-related deaths are due to the spread of tumor cells in the body. Therefore, the search for markers of aggressive disease and tumor cell dissemination is ongoing, along with ways to prevent or treat invasive spread. Matrix metalloproteinases (MMPs) have long been regarded as potential targets for anticancer therapy. In humans, the MMPs are a family of 24 secreted endopeptidases that can collectively degrade all protein components of the extracellular matrix. Although they play important roles in normal physiological processes, including wound healing and embryonic development, they are also often found to be expressed at higher levels in cancer tissues compared with their normal counterparts. Numerous studies have demonstrated their involvement in tumor invasion and metastasis in various cancer types [1]. The tumorspecific upregulation of MMPs, together with their prominent roles in cancer dissemination and a high protein sequence homology at their catalytic sites, led to the development in the 1980s and 1990s of smallmolecule active site-directed inhibitors for cancer therapy [2]. Initial preclinical studies had generated promising findings and these broadspectrum inhibitors went into clinical trials accompanied by great optimism. Unfortunately, these trials proved disappointing, with some of the inhibitors in fact promoting tumor progression and decreasing survival rates in some types of cancer [3,4]. Subsequent in-depth analysis of in vitro and in vivo studies revealed a number of factors that may in part explain the limited beneficial effects of treatment with broad-spectrum MMP inhibitors. The discrepancy in preclinical and clinical efficacy of these drugs is most probably related to the different disease stages used. While in vivo animal studies were most