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The development of steroid sulfatase iInhibitors for hormone-dependent cancer therapy


Reference:

Day, J. M., Purohit, A., Tutill, H. J., Foster, P. A., Woo, L. W. L., Potter, B. V. L. and Reed, M. J., 2009. The development of steroid sulfatase iInhibitors for hormone-dependent cancer therapy. In: Bradlow, H. L. and Carruba, G., eds. Steroid Enzymes and Cancer. Vol. 1155. Blackwell Publishing, pp. 80-87. (Annals of the New York Academy of Sciences)

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Official URL:

http://dx.doi.org/10.1111/j.1749-6632.2008.03677.x

Abstract

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.

Details

Item Type Book Sections
CreatorsDay, J. M., Purohit, A., Tutill, H. J., Foster, P. A., Woo, L. W. L., Potter, B. V. L. and Reed, M. J.
EditorsBradlow, H. L.and Carruba, G.
DOI10.1111/j.1749-6632.2008.03677.x
Uncontrolled Keywordssteroid sulfatase (sts), breast cancer, ovarian cancer, endometrial cancer, sulfatase inhibitor, prostate cancer
DepartmentsFaculty of Science > Pharmacy & Pharmacology
StatusPublished
ID Code13978
Additional InformationProceedings paper from the 9th Advanced Course on Steroid Enzymes and Cancer. Erice, Italy, 3-8 May, 2008

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