Protease inhibitors: role and potential therapeutic use in human cancer.
Proteases and protease inhibitors have been increasingly recognised as important factors in the physiopathology of human diseases, and our understanding of their role in cancer has dramatically increased over the last decade. We have obtained causal evidence linking proteases to tumour invasion and metastasis, and have become aware of genuine mechanisms used by tumour cells to optimise the use of proteases in the pericellular matrix. Many synthetic and natural inhibitors of these proteases have also been characterised, and their mechanisms of interaction with their corresponding enzymes are progressively unveiled as the X-ray crystal structures of these enzymes and their inhibitors are now reported. It has also become evident that many of these inhibitors, in addition to preventing the dissemination of cancer cells, have an inhibitory effect on tumour growth. Thus protease inhibitors are emerging as potentially therapeutic tools to treat cancer. In this article, recent studies on the role of proteases and their inhibitors in cancer are reviewed, and current ideas on their potential use as therapeutic agents are discussed.
Department of Pediatrics, Childrens Hospital Los Angeles, California.
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DeClerck
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Imren
D000818:Animals; D001665:Binding Sites; D010450:Endopeptidases / Q000502:physiology; D006801:Humans; D008666:Metalloendopeptidases / Q000502:physiology; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D011480:Protease Inhibitors / Q000627:therapeutic use*; D012697:Serine Endopeptidases / Q000502:physiology
D011480:Protease Inhibitors; D010450:Endopeptidases; D012697:Serine Endopeptidases; D008666:Metalloendopeptidases