Preclinical evaluation of aromatase inhibitors antitumor activity

The aromatase is an enzymatic complex responsible for the conversion of and rogens into estrogens; there hormones are important in development, reprodu ction, but also in the growth of estrogen-dependent cancer This enzyme is p resent in 60-70% of the breast cancer The aromatase inhibitors are importan t drugs in the breast cancer treatment of postmenopausal women. In order to study their in vivo activity, animal models have been developed, e.g. rat with tumour induced by 7,12-dimethylbenz[a]anthracene, PMSG-primed immature rat or athymic nude mice with aromatase transfected MCF-7 xenograft. In th is review we were interested in preclinical results obtained with both clas ses: steroidal and non steroidal inhibitors. The former group, as substrate analogs fomestane or exemestane, are irreversible, selective and longlasti ng inhibitors of aromatase. The nan steroidal molecules, as letrozole or an astrozole, are reversible inhibitors with high affinity. Finally, the knowl edge of the enzyme active site, with molecular modeling and site-directed m utagenesis, could be useful to develop new inhibitor families, more specifi c and potent in vivo.