Extracellular proteases as targets for treatment of cancer metastases.
Metastasis, the dissemination of tumor cells to distant organs, is often associated with fatal outcome in cancer patients. Formation of metastasis requires degradation of extracellular matrices and several families of proteases have been implicated in this process, including matrix metalloproteinases (MMPs), serine and cysteine proteases. Inhibition of these enzymes in animal models of metastasis has shown impressive therapeutic effects. This report discusses the various approaches used for enzyme inhibition and describes new developments in drug design for inhibition of proteases in metastatic disease.
Lee
Mijoon
M
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA.
Fridman
Rafael
R
Mobashery
Shahriar
S
D000818:Animals; D015195:Drug Design; D016326:Extracellular Matrix Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D009362:Neoplasm Metastasis / Q000188:drug therapy*; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D010447:Peptide Hydrolases / Q000378:metabolism*; D011480:Protease Inhibitors / Q000737:chemistry / Q000627:therapeutic use*
D016326:Extracellular Matrix Proteins; D011480:Protease Inhibitors; D010447:Peptide Hydrolases