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Preclinical and Clinical Studies of MMP Inhibitors in Cancer
Author(s) -
DRUMMOND ALAN H.,
BECKETT PAUL,
BROWN PETER D.,
BONE ELISABETH A.,
DAVIDSON ALAN H.,
GALLOWAY W. ALAN,
GEARING ANDY J.H.,
HUXLEY PHIL,
LABER DAVID,
MCCOURT MATTHEW,
WHITTAKER MARK,
WOOD L. MICHAEL,
WRIGHT ANNETTE
Publication year - 1999
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1999.tb07688.x
Subject(s) - matrix metalloproteinase , matrix metalloproteinase inhibitor , angiogenesis , cancer , medicine , animal studies , broad spectrum , pharmacology , cancer therapy , cancer research , bioinformatics , biology , chemistry , combinatorial chemistry
The role of matrix metalloproteinases in tumor angiogenesis and growth is now well recognized for models of both human and animal cancer. Clinical studies currently under way with the prototype matrix metalloproteinase inhibitor, marimastat, will establish whether inhibitors of these enzymes are of benefit in the treatment of different types of human cancer. On chronic therapy in humans, marimastat induces a reversible tendinitis that can also be detected in certain animal species. This paper compares the ability of broad‐spectrum and various types of selective matrix metalloproteinase inhibitors to induce tendinitis and to exhibit anticancer effects in an animal cancer model. Under conditions in which both systemic exposure and inhibitor potency are controlled, selective inhibitors are less pro‐tendinitic, but are weaker anticancer agents than broad‐spectrum agents such as marimastat. The clinical relevance of these findings is discussed.