MMP inhibitors: experimental and clinical studies.
Matrix metalloproteases (MMPs) are a family of structurally related enzymes that are capable of degrading proteins of the extracellular matrix. These enzymes play a role in tissue remodelling associated with both physiological and pathogenic processes. A high expression of MMPs is associated with cancer malignancy: it is related to the tumor's ability to metastasize and to the process of angiogenesis. Treatment with MMP inhibitors alone or in combination with cytotoxic therapy is an interesting novel approach to control tumor progression. The expected mechanism of action of these compounds and the difference in side effects compared to cytotoxic drugs make the definition of endpoints and the assessment of response difficult. Furthermore, it is not yet clear whether tumor vascularization or, more specifically, MMP expression/activation should be a criterion of eligibility for this kind of treatment. This review provides an overview of the characteristics of MMPs and their role in tumor progression, metastasis and angiogenesis. Preclinical and clinical studies with synthetic MMP inhibitors are described. The presence of MMPs in biological fluids of patients and their use in prognostic evaluation and in determining the efficacy of treatment with MMP inhibitors is discussed.
Belotti
D
D
Laboratory of the Biology and Treatment of Metastasis, Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
Paganoni
P
P
Giavazzi
R
R
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001381:Azepines / Q000494:pharmacology; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D061965:Matrix Metalloproteinase Inhibitors; D009930:Organic Chemicals; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D013876:Thiophenes / Q000494:pharmacology
D000970:Antineoplastic Agents; D001381:Azepines; D006877:Hydroxamic Acids; D061965:Matrix Metalloproteinase Inhibitors; D009930:Organic Chemicals; D011480:Protease Inhibitors; D013876:Thiophenes; C113282:prinomastat; D010649:Phenylalanine; C080985:batimastat; C100342:marimastat