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

Joanna M. Day, Atul Purohit, Helena J. Tutill, Paul A. Foster, L. W. Lawrence Woo, Barry V. L. Potter, Michael J. Reed

Research output: Chapter in Book/Report/Conference proceedingChapter

39 Citations (Scopus)

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.
Original languageEnglish
Title of host publicationSteroid Enzymes and Cancer
EditorsH. L. Bradlow, G. Carruba
PublisherWiley-Blackwell
Pages80-87
Volume1155
DOIs
Publication statusPublished - 2009
Event9th Advanced Course on Steroid Enzymes and Cancer - Erice, Italy
Duration: 1 Jan 2009 → …

Publication series

NameAnnals of the New York Academy of Sciences
PublisherBlackwell Publishing

Conference

Conference9th Advanced Course on Steroid Enzymes and Cancer
CountryItaly
CityErice
Period1/01/09 → …

Keywords

  • steroid sulfatase (STS)
  • breast cancer
  • ovarian cancer
  • endometrial cancer
  • sulfatase inhibitor
  • prostate cancer

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    Day, J. M., Purohit, A., Tutill, H. J., Foster, P. A., Woo, L. W. L., Potter, B. V. L., & Reed, M. J. (2009). The development of steroid sulfatase iInhibitors for hormone-dependent cancer therapy. In H. L. Bradlow, & G. Carruba (Eds.), Steroid Enzymes and Cancer (Vol. 1155, pp. 80-87). (Annals of the New York Academy of Sciences). Wiley-Blackwell. https://doi.org/10.1111/j.1749-6632.2008.03677.x