MATRIX METALLOPROTEASES IN HEAD AND NECK CANCER

Abstract: Matrix metalloproteases (MMPs) are a collection of enzymes capable of cleaving extracellular matrix components, growth factors, and cell-surface receptors. MMPs modulate most aspects of tumorigenesis and are highly expressed in can-cer compared with normal tissues. Preclinical studies have dem-onstrated that head and neck squamous cell carcinomas (HNSCCs) express high levels of MMPs in vivo and that inhibi-tion of these enzymes in vitro and in mouse models decreases invasion and metastasis. However, the clinical trials for MMP inhibitors have failed to demonstrate a significant survival advantage in most cancers. The disparity between preclinical and clinical studies has led to the reevaluation of how MMP func-tions in cancer and the design of clinical trials for molecularly tar-geted agents. Mouse model data and analysis of HNSCC tumor specimens suggests that membrane type-1 MMP (MT1-MMP) may be a critical enzyme in tumor cell invasion and survival in vivo. This accumulated data provide evidence for development of selective MT1-MMP inhibitors as therapy in HNSCC