title: Antiestrogens: structure-activity relationships and use in breast cancer treatment.
abstract: About 70% of breast tumors express estrogen receptor alpha (ERα), which mediates the proliferative effects of estrogens on breast epithelial cells, and are candidates for treatment with antiestrogens, steroidal or non-steroidal molecules designed to compete with estrogens and antagonize ERs. The variable patterns of activity of antiestrogens (AEs) in estrogen target tissues and the lack of systematic cross-resistance between different types of molecules have provided evidence for different mechanisms of action. AEs are typically classified as selective estrogen receptor modulators (SERMs), which display tissue-specific partial agonist activity (e.g. tamoxifen and raloxifene), or as pure AEs (e.g. fulvestrant), which enhance ERα post-translational modification by ubiquitin-like molecules and accelerate its proteasomal degradation. Characterization of second- and third-generation AEs, however, suggests the induction of diverse ERα structural conformations, resulting in variable degrees of receptor downregulation and different patterns of systemic properties in animal models and in the clinic.
authors.affiliation: Institute for Research in Immunology and CancerUniversité de Montréal, Montréal, Québec, Canada.|Department of Biochemistry and Molecular MedicineUniversité de Montréal, Montréal, Québec, Canada.
authors.forename: T
authors.initials: T
authors.lastname: Traboulsi
authors.affiliation: Institute for Research in Immunology and CancerUniversité de Montréal, Montréal, Québec, Canada.
authors.forename: M
authors.initials: M
authors.lastname: El Ezzy
authors.affiliation: Department of ChemistryMcGill University, Montréal, Québec, Canada.
authors.forename: J L
authors.initials: JL
authors.lastname: Gleason
authors.affiliation: Institute for Research in Immunology and CancerUniversité de Montréal, Montréal, Québec, Canada sylvie.mader@umontreal.ca.|Department of Biochemistry and Molecular MedicineUniversité de Montréal, Montréal, Québec, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Mader
mesh_terms: D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000473:pathology; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D019008:Drug Resistance, Neoplasm; D004965:Estrogen Antagonists / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D009154:Mutation; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020845:Selective Estrogen Receptor Modulators / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D013329:Structure-Activity Relationship; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D011960:Receptors, Estrogen; D020845:Selective Estrogen Receptor Modulators
keywords: SUMOylation; antiestrogens; breast cancer; estrogen receptors; ubiquitination