title: 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.affiliation: Cancer Research UK Laboratories, Division of Cancer, Imperial College, Du Cane Road, London W12 0NN, UK. c.palmieri@imperial.ac.uk
authors.forename: Carlo
authors.initials: C
authors.lastname: Palmieri
authors.forename: Adam
authors.initials: A
authors.lastname: Januszewski
authors.forename: Susie
authors.initials: S
authors.lastname: Stanway
authors.forename: R Charles
authors.initials: RC
authors.lastname: Coombes
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D017322:Clinical Trials, Phase II as Topic; D019314:Dehydroepiandrosterone Sulfate / Q000378:metabolism; D004958:Estradiol / Q000031:analogs & derivatives / Q000627:therapeutic use; D004970:Estrone / Q000031:analogs & derivatives / Q000378:metabolism / Q000627:therapeutic use; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy*; D043266:Steryl-Sulfatase / Q000037:antagonists & inhibitors*; D013451:Sulfonic Acids / Q000627:therapeutic use*; D013629:Tamoxifen / Q000627:therapeutic use
chemical_list: D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D013451:Sulfonic Acids; D013629:Tamoxifen; D000077267:Fulvestrant; D004970:Estrone; C520511:irosustat; D004958:Estradiol; D019314:Dehydroepiandrosterone Sulfate; D043266:Steryl-Sulfatase; C017296:estrone sulfate