ABSTRACT
T he num ber o f m em bers in m atrix m etalloproteinase (M M P) family is rapidly increasing. It is ev ident th a t several m em bers in this fam ily co n trib u te to cancer metastasis. B oth invasion and angiogenesis are essential in tu m o r progression, and th e m em bers o f the M M P -fam ily are im p o rtan t in bo th o f these cancer-related b u t n o t cancer-specific p h en o m ena. M ost clinical data published su p p o rt the concept th a t in particu lar gelatinases A and В (M M P -2 and - 9 ) are linked to the aggressive behavior o f cancer. T h e aggressive clinical course has been linked to the expression o f a M M P in a surprisingly large variety o f cancer. T h e overexpression o f gelatinases has especially tu rn ed o u t to be prognostic for survival o r to corre late w ith grade o r stage in several cancer types. M M P -2 has even been show n to pred ic t relapse du rin g an tiestrogen ad juvant chem otherapy in breast carcinom a. T h e role o f T IM P s (tissue inh ib ito rs o f m etalloproteinases) is m ore com plex in d e term in ing the clinical course o f differ en t types o f cancers. In som e tum ors th e relative am o u n t o f m etalloproteinase and its in h ib ito r is associated w ith aggressive behavior o f the disease. T h e m ain data, however, states for the tim e being th a t aggressive cancers also overexpress T IM P s, w hich m ay be associated w ith tu m o r progression ra ther th an w ith an in d o len t clinical course o f a tum or. T h ere seems to be a larger variation betw een d ifferent cancer types in this context. Studies to con tro l tu m o r invasion and angiogenesis by using syn thetic inh ib ito rs for M M P s have so far show n little clinical prom ise. A ngiogenesis is con tro lled by m any inh ib ito rs and activators. It seems difficult to be able to affect it w ith very specific tools. T h is does n o t ru le o u t th a t co m b in a tio n s o f d iffe ren t an tiang iogenic agents m ay be useful in the fu tu re as trea tm en t o p tions fo r cancer patients. M M P Is are now stud ied in m any clinical trials, and the results o f the ongoing studies will define th e ir role in cancer treatm ent.
