An in vitro model showing adaptation to long-term oestrogen deprivation highlights the clinical potential for targeting kinase pathways in combination with aromatase inhibition

• Published in: Steroids Vol. 76; no. 8; pp. 772 - 776
• Main Authors: Martin, L.-A., Ghazoui, Z., Weigel, M.T., Pancholi, Sunil, Dunbier, A., Johnston, Stephen, Dowsett, M.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Kidlington Elsevier Inc 01.07.2011; Elsevier
• Subjects: Anastrozole; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Aromatase inhibitor; Aromatase Inhibitors - therapeutic use; Biological and medical sciences; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - enzymology; Cell Line, Tumor; Drug Resistance, Neoplasm; Endocrine resistance; Estradiol - analogs & derivatives; Estradiol - pharmacology; Estrogens - metabolism; Female; Fulvestrant; Fundamental and applied biological sciences. Psychology; Gene Expression Profiling; Gynecology. Andrology. Obstetrics; Humans; Insulin-Like Growth Factor I - metabolism; Kinases; Mammary gland diseases; Medical sciences; Models, Biological; Nitriles - therapeutic use; Oestrogen receptor; Postmenopause; Receptors, Estrogen - genetics; Receptors, Estrogen - metabolism; Recurrence; Triazoles - therapeutic use; Tumors; Vertebrates: endocrinology; Endocrine resistance; Breast cancer; Aromatase inhibitor; Kinases; Oestrogen receptor; Breast disease; Targeting; Enzyme; Estrogen; Malignant tumor; Estrogen synthase; In vitro; Long term; Ovarian hormone; Resistance; Mammary gland diseases; Models; Inhibition; Sex steroid hormone; Cancer; Adaptation; Biological receptor
• ISSN: 0039-128X; 1878-5867
• DOI: 10.1016/j.steroids.2011.02.035

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.