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Steroid sulfatase inhibitors: promising new tools for breast cancer therapy?

Abstract
Inhibition of aromatase is currently well-established as the major treatment option of hormone-dependent breast cancer in postmenopausal women. However, despite the effects of aromatase inhibitors in both early and metastatic breast cancer, endocrine resistance may cause relapses of the disease and progression of metastasis. Thus, driven by the success of manipulating the steroidogenic enzyme aromatase, several alternative enzymes involved in steroid synthesis and metabolism have recently been investigated as possible drug targets. One of the most promising targets is the steroid sulfatase (STS) which converts steroid sulfates like estrone sulfate (E1S) and dehydroepiandrosterone sulfate (DHEAS) to estrone (E1) and dehydroepiandrosterone (DHEA), respectively. Estrone and DHEA may thereafter be used for the synthesis of more potent estrogens and androgens that may eventually fuel hormone-sensitive breast cancer cells. The present review summarizes the biology behind steroid sulfatase and its inhibition, the currently available information derived from basic and early clinical trials in breast cancer patients, as well as ongoing research. Article from the Special Issue on Targeted Inhibitors.
AuthorsJürgen Geisler, Hironobu Sasano, Shiuan Chen, Atul Purohit
JournalThe Journal of steroid biochemistry and molecular biology (J Steroid Biochem Mol Biol) Vol. 125 Issue 1-2 Pg. 39-45 (May 2011) ISSN: 1879-1220 [Electronic] England
PMID21356310 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
CopyrightCopyright © 2011 Elsevier Ltd. All rights reserved.
Chemical References
  • Androgens
  • Aromatase Inhibitors
  • Enzyme Inhibitors
  • Estrogens
  • Steryl-Sulfatase
Topics
  • Androgens (biosynthesis)
  • Aromatase Inhibitors (therapeutic use)
  • Breast Neoplasms (drug therapy, enzymology)
  • Clinical Trials as Topic
  • Enzyme Inhibitors (chemistry, therapeutic use)
  • Estrogens (biosynthesis)
  • Female
  • Humans
  • Molecular Structure
  • Steryl-Sulfatase (antagonists & inhibitors, metabolism)

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