title: An in vitro model showing adaptation to long-term oestrogen deprivation highlights the clinical potential for targeting kinase pathways in combination with aromatase inhibition.
abstract: Aromatase inhibitors (AI) have improved the treatment of oestrogen receptor positive (ER+) breast cancer. Despite the efficacy of these agents over 40% of patients relapse with endocrine resistant disease. Here we describe an in vitro model of acquired resistance to long-term oestrogen deprivation (LTED). The LTED cells retain expression of the ER and appear hypersensitive to oestrogen as a result of altered kinase activity. Furthermore analysis of temporal changes in gene expression during the acquisition of resistance highlight growth factor receptor pathways as key mediators of this adaptive process.
authors.affiliation: Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, Fulham Road, London SW36JB, UK. lesley-ann.martin@icr.ac.uk
authors.forename: L-A
authors.initials: LA
authors.lastname: Martin
authors.forename: Z
authors.initials: Z
authors.lastname: Ghazoui
authors.forename: M T
authors.initials: MT
authors.lastname: Weigel
authors.forename: Sunil
authors.initials: S
authors.lastname: Pancholi
authors.forename: A
authors.initials: A
authors.lastname: Dunbier
authors.forename: Stephen
authors.initials: S
authors.lastname: Johnston
authors.forename: M
authors.initials: M
authors.lastname: Dowsett
mesh_terms: D000077384:Anastrozole; D000971:Antineoplastic Combined Chemotherapy Protocols; D017209:Apoptosis; D047072:Aromatase Inhibitors / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D000077267:Fulvestrant; D020869:Gene Expression Profiling; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008954:Models, Biological; D009570:Nitriles / Q000627:therapeutic use; D017698:Postmenopause; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D012008:Recurrence; D014230:Triazoles / Q000627:therapeutic use
chemical_list: D047072:Aromatase Inhibitors; D004967:Estrogens; D009570:Nitriles; D011960:Receptors, Estrogen; D014230:Triazoles; D000077267:Fulvestrant; D000077384:Anastrozole; D004958:Estradiol; D007334:Insulin-Like Growth Factor I