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

• Published in: The Journal of steroid biochemistry and molecular biology Vol. 125; no. 1; pp. 39 - 45
• Main Authors: Geisler, Jürgen, Sasano, Hironobu, Chen, Shiuan, Purohit, Atul
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.05.2011
• Subjects: Androgens; Androgens - biosynthesis; Aromatase inhibitors; Aromatase Inhibitors - therapeutic use; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - enzymology; Clinical Trials as Topic; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - therapeutic use; Estrogens; Estrogens - biosynthesis; Female; Humans; Irosustat; Molecular Structure; Steryl-Sulfatase - antagonists & inhibitors; Steryl-Sulfatase - metabolism; STX 213; STX 64; STX 681; Sulfatase inhibitors; Androgens; STX 681; Estrogens; STX 213; Sulfatase inhibitors; Breast cancer; STX 64; Irosustat; Aromatase inhibitors
• ISSN: 0960-0760; 1879-1220
• DOI: 10.1016/j.jsbmb.2011.02.002

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.