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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.

Original publication

DOI

10.1111/j.1749-6632.2008.03677.x

Type

Conference paper

Publication Date

02/2009

Volume

1155

Pages

80 - 87

Keywords

Breast Neoplasms, Cell Line, Tumor, Endometrial Neoplasms, Enzyme Inhibitors, Female, Humans, Male, Neoplasms, Hormone-Dependent, Prostatic Neoplasms, RNA, Messenger, Reverse Transcriptase Polymerase Chain Reaction, Steryl-Sulfatase