Day Joanna M, Purohit Atul, Tutill Helena J, Foster Paul A, Woo L W Lawrence, Potter Barry V L, Reed Michael J
Endocrinology and Metabolic Medicine and Sterix Ltd., Imperial College London, St. Mary's Hospital, London, W2 1NY, United Kingdom.
Ann N Y Acad Sci. 2009 Feb;1155:80-7. doi: 10.1111/j.1749-6632.2008.03677.x.
Steroid sulfatase (STS) regulates the hydrolysis of steroid sulfates to their unconjugated forms. Estrone sulfate and dehydroepiandrosterone sulfate can be hydrolyzed by STS to estrone and dehydroepiandrosterone, respectively, with these steroids being the precursors for the synthesis of more biologically active estrogens or androgens. A number of potent STS inhibitors have now been developed including STX64, which entered a phase I trial for the treatment of postmenopausal women with advanced metastatic hormone-dependent breast cancer. The results from this phase I trial were encouraging, suggesting that STS inhibitors may also have a role in the treatment of other hormone-dependent cancers including those of the endometrium, ovary, and prostate. In this paper the potential use of STS inhibitors to treat these hormone-dependent cancers is reviewed. In addition, results from in vitro studies show that Ishikawa endometrial cancer cells, OVCAR-3 ovarian cancer cells, and LNCaP prostate cancer cells all possess significant STS activity. Furthermore, STS activity in these cells can be almost completely inhibited by STX64 or the second-generation STS inhibitor, STX213. Results from these investigations therefore suggest that STS inhibitors could have therapeutic potential for the treatment of a range of hormone-dependent cancers.
类固醇硫酸酯酶（STS）调节类固醇硫酸盐水解为其未结合形式。硫酸雌酮和硫酸脱氢表雄酮可分别被STS水解为雌酮和脱氢表雄酮，这些类固醇是合成更具生物活性的雌激素或雄激素的前体。目前已开发出多种有效的STS抑制剂，包括STX64，它已进入治疗晚期转移性激素依赖性乳腺癌绝经后妇女的I期试验。该I期试验的结果令人鼓舞，表明STS抑制剂在治疗包括子宫内膜癌、卵巢癌和前列腺癌在内的其他激素依赖性癌症中可能也有作用。本文综述了STS抑制剂治疗这些激素依赖性癌症的潜在用途。此外，体外研究结果表明，石川子宫内膜癌细胞、OVCAR-3卵巢癌细胞和LNCaP前列腺癌细胞均具有显著的STS活性。此外，STX64或第二代STS抑制剂STX213几乎可以完全抑制这些细胞中的STS活性。因此，这些研究结果表明，STS抑制剂在治疗一系列激素依赖性癌症方面可能具有治疗潜力。
