Oncology Drug Discovery Group, Section of Investigative Medicine, Imperial College London, Hammersmith Hospital, London W12 0NN, UK.
J Endocrinol. 2012 Feb;212(2):99-110. doi: 10.1530/JOE-11-0266. Epub 2011 Aug 22.
Estrogens and androgens are instrumental in the maturation of many hormone-dependent cancers. Consequently, the enzymes involved in their synthesis are cancer therapy targets. One such enzyme, steroid sulfatase (STS), hydrolyses estrone sulfate, and dehydroepiandrosterone sulfate to estrone and dehydroepiandrosterone respectively. These are the precursors to the formation of biologically active estradiol and androstenediol. This review focuses on three aspects of STS inhibitors: 1) chemical development, 2) biological activity, and 3) clinical trials. The aim is to discuss the importance of estrogens and androgens in many cancers, the developmental history of STS inhibitor synthesis, the potency of these compounds in vitro and in vivo and where we currently stand in regards to clinical trials for these drugs. STS inhibitors are likely to play an important future role in the treatment of hormone-dependent cancers. Novel in vivo models have been developed that allow pre-clinical testing of inhibitors and the identification of lead clinical candidates. Phase I/II clinical trials in postmenopausal women with breast cancer have been completed and other trials in patients with hormone-dependent prostate and endometrial cancer are currently active. Potent STS inhibitors should become therapeutically valuable in hormone-dependent cancers and other non-oncological conditions.
雌激素和雄激素在许多激素依赖性癌症的成熟过程中起着重要作用。因此，参与其合成的酶是癌症治疗的靶点。其中一种酶是甾体硫酸酯酶（STS），它将雌酮硫酸酯和脱氢表雄酮硫酸酯分别水解为雌酮和脱氢表雄酮。这些是生物活性雌二醇和雄烯二酮形成的前体。本综述重点介绍 STS 抑制剂的三个方面：1）化学发展，2）生物学活性，3）临床试验。目的是讨论雌激素和雄激素在许多癌症中的重要性、STS 抑制剂合成的发展历史、这些化合物在体外和体内的效力以及我们在这些药物的临床试验方面的现状。STS 抑制剂可能在激素依赖性癌症的治疗中发挥重要的未来作用。已经开发了新的体内模型，允许对抑制剂进行临床前测试，并确定临床候选药物的先导。已经完成了绝经后患有乳腺癌的妇女的 I/II 期临床试验，目前正在对患有激素依赖性前列腺癌和子宫内膜癌的患者进行其他临床试验。在激素依赖性癌症和其他非肿瘤疾病中，有效的 STS 抑制剂应该具有治疗价值。
