Matrix metalloproteinases as therapeutic targets in cancer.
Degradation of extracellular matrix is crucial for malignant tumor growth, invasion, metastasis and angiogenesis. Matrix metalloproteinases (MMPs) are a family of zinc-dependent neutral endopeptidases collectively capable of degrading essentially all matrix components. Elevated levels of distinct MMPs can be detected in tumor tissue or serum of patients with advanced cancer, and their role as prognostic indicators in cancer has been widely examined. In addition, therapeutic intervention in tumor growth and invasion based on inhibition of MMP activity is under intensive investigation and several MMP inhibitors (MMPIs) are in clinical cancer trials. Even though results of the first clinical trials in advanced cancer have been mostly disappointing, there are also positive results. Recent observations show, that certain MMPs limit tumor growth. Therefore, identification of proper MMPs for therapeutic intervention with array-based molecular classifications of tumors and targeting these with more specific MMPIs in combination with conventional chemotherapy is expected to provide a feasible approach for cancer therapy. MMPIs represent a totally different therapeutic modality from proven anti-cancer drugs and thus traditional approaches to evaluate drug efficiency cannot be used without modification. In this review, we discuss the current view on the feasibility of MMPs as targets for therapeutic intervention in cancer.
Vihinen
Pia
P
Department of Oncology and Radiotherapy, Turku University Hospital, Kiinamyllynkatu 4-8, FIN-20520 Turku, Finland. pia.vihinen@tyks.fi
Ala-aho
Risto
R
Kähäri
Veli-Matti
VM
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D016376:Oligonucleotides, Antisense