Brodie A M, Santen R J
Crit Rev Oncol Hematol. 1986;5(4):361-96. doi: 10.1016/s1040-8428(86)80003-8.
Approximately one third of human breast carcinomas are hormone dependent and regress upon reduction of circulating estrogen levels. Traditional treatment strategies utilized surgical ablative methods to lower estrogen concentrations as treatment of breast cancer. Currently, investigative emphasis is focused upon development of highly specific antiestrogens and inhibitors of estrogen production. The enzyme, aromatase, as the terminal step in estrogen biosynthesis, is a logical target for blockade with potent and specific inhibitors. The earliest available aromatase antagonist, aminoglutethimide, suppresses estrogen production to the same extent as surgical ablation and is an effective treatment for breast cancer. Aminoglutethimide, however, blocks other cytochrome P-450-mediated steroid hydroxylations, requires concomitant glucocorticoid administration, and is associated with initial side effects. Several more specific inhibitors by destroying aromatase irreversibly as well as by competitive inhibition. One of these, 4-hydroxy-androstenedione, has been intensively studied in animals and is undergoing clinical trial. New data regarding these inhibitors further emphasize the key role of aromatase in estrogen production and the practical utility of blocking this enzyme.
大约三分之一的人类乳腺癌是激素依赖性的，会随着循环雌激素水平的降低而消退。传统的治疗策略采用手术切除方法来降低雌激素浓度以治疗乳腺癌。目前，研究重点集中在开发高度特异性的抗雌激素药物和雌激素生成抑制剂。芳香化酶作为雌激素生物合成的最后一步，是用强效特异性抑制剂进行阻断的合理靶点。最早可用的芳香化酶拮抗剂氨鲁米特，可将雌激素生成抑制到与手术切除相同的程度，是治疗乳腺癌的有效方法。然而，氨鲁米特会阻断其他细胞色素P-450介导的类固醇羟基化反应，需要同时给予糖皮质激素，并且会出现初始副作用。还有几种更特异性的抑制剂，它们通过不可逆地破坏芳香化酶以及竞争性抑制来发挥作用。其中一种，4-羟基雄烯二酮，已在动物身上进行了深入研究，正在进行临床试验。关于这些抑制剂的新数据进一步强调了芳香化酶在雌激素生成中的关键作用以及阻断该酶的实际应用价值。
