Bulletin du Cancer


Preclinical evaluation of aromatase inhibitors antitumor activity Volume 87, special issue 12, Numéro spécial, Décembre 2000


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The aromatase is an enzymatic complex responsible for the conversion of androgens into estrogens; these hormones are important in development, reproduction, but also in the growth of estrogen-dependent cancer. This enzyme is present in 60-70% of the breast cancer. The aromatase inhibitors are important 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 this review, we were interested in preclinical results obtained with both classes: steroidal and non steroidal inhibitors. The former group, as substrate analogs formestane or exemestane, are irreversible, selective and long-lasting inhibitors of aromatase. The non steroidal molecules, as letrozole or anastrozole, are reversible inhibitors with high affinity. Finally, the knowledge of the enzyme active site, with molecular modeling and site-directed mutagenesis, could be useful to develop new inhibitor families, more specific and potent in vivo.