Irosustat: a first-generation steroid sulfatase inhibitor in breast cancer.

Abstract

Endocrine therapy is a key modality in the management of breast cancer, with current options for postmenopausal women including tamoxifen, aromatase inhibitors and fulvestrant. Unfortunately, in spite of these advances, many women still relapse or progress on endocrine therapy. Given that resistance (de novo or acquired resistance) is a major limiting factor in the use of endocrine therapy, additional endocrine therapies with novel methods of action are required. Steroid sulfatase, which is responsible for the conversion of estrone sulfate to estrone, as well as dehydroepiandrosterone sulfate to dehydroepiandrosterone, has been implicated in endocrine resistance. In this article, we summarize the preclinical and clinical data to support the potential role of steroid sulfatase in breast cancer, as well as the current data on the first available steroid sulfatase inhibitor named irosustat (STX64; 667 Coumate; BN83495), and discuss its potential clinical development.

• Authors: Carlo Palmieri, Adam Januszewski, Susie Stanway, R Charles Coombes
• Journal: Expert review of anticancer therapy (Expert Rev Anticancer Ther) Vol. 11 Issue 2 Pg. 179-83 (Feb 2011) ISSN: 1744-8328 [Electronic] England
• PMID: 21342037 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Antineoplastic Agents, Hormonal
• Aromatase Inhibitors
• Sulfonic Acids
• Tamoxifen
• Fulvestrant
• Estrone
• irosustat
• Estradiol
• Dehydroepiandrosterone Sulfate
• Steryl-Sulfatase
• estrone sulfate

Topics

• Antineoplastic Agents, Hormonal (therapeutic use)
• Aromatase Inhibitors (therapeutic use)
• Breast Neoplasms (drug therapy)
• Clinical Trials, Phase II as Topic
• Dehydroepiandrosterone Sulfate (metabolism)
• Estradiol (analogs & derivatives, therapeutic use)
• Estrone (analogs & derivatives, metabolism, therapeutic use)
• Female
• Fulvestrant
• Humans
• Neoplasms, Hormone-Dependent (drug therapy)
• Steryl-Sulfatase (antagonists & inhibitors)
• Sulfonic Acids (therapeutic use)
• Tamoxifen (therapeutic use)