Matrix metalloproteinases in the pathophysiology and progression of gynecological malignancies: could their inhibition be an effective therapeutic approach?
BACKGROUND
MMPs are a group of zinc-dependent endopeptidases implicated in the degradation of extracellular matrix components. Angiogenesis, wound healing and tissue remodeling are the main processes in which MMPs have been implicated. MMPs also seem to play a role in the pathophysiological processes during tumorigenesis and are thought to have predictive value for clinical outcome. Alterations in the regulation of MMP expression are considered to be of significant importance in the development and progression of gynecological malignancies.


OBJECTIVE
This study provides a literature review on the involvement of MMPs in the development and progression of gynecological malignancies, their clinical significance and the potential use of natural and/or synthetic MMP Inhibitors (MMPIs) as a more targeted therapeutic approach to these neoplasms.


CONCLUSIONS
There is mounting evidence that MMPs play an important role in development and progression of gynecological malignancies. Current results provide the basis for further investigation of their role in malignancies, the therapeutic potential of their inhibition and the side-effects that can be expected from the modulation of matrix remodeling during therapeutic intervention. Focused research on the combination of MMPIs with cytotoxic and/or antiangiogenic compounds might provide the key to more successful therapeutic approaches towards gynecological and other malignancies.
Memtsas
Vassilios
V
National & Kapodistrian University of Athens, Medical School, Department of Forensic Medicine & Toxicology, GR-11527, Athens, Greece.
Zarros
Apostolos
A
Theocharis
Stamatios
S
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005833:Genital Neoplasms, Female / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000503:physiopathology
D000970:Antineoplastic Agents; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases