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Mechanisms of resistance to aromatase inhibitors

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Dowsett, M., Martin, L. A., Smith, I., Johnston, S. (2005) Mechanisms of resistance to aromatase inhibitors. JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 95 (1-5). pp. 167-172. ISSN 0960-0760

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Abstract

Mechanisms of resistance to aromatase inhibitors Aromatase inhibitors are rapidly becoming the first choice for hormonal treatment of steroid receptor positive breast cancer in postmenopausal women. An understanding of the resistance mechanisms to these agents is, therefore, important for the appropriate delivery of treatment to responsive patients and the rational development of new agents targeted at the resistance pathways. De novo resistance appears to be a quantitative rather than qualitative phenomenon with virtually all oestrogen receptor positive tumours showing an anti-proliferative response to the aromatase inhibitor anastrozole. While the expression of type I growth factor receptors reduces response to tamoxifien this appears to have little detrimental effect on response to aromatase inhibitors. Studies of acquired resistance in vitro have indicated that acquisition of hypersensitivity to oestrogenic stimulation is a key mechanism that is dependent on enhanced cross-talk of growth factor and oestrogen signaling pathways. Collection of resistant biopsy tissues from patients is important to determine if this mechanism is clinically relevant. (c) 2005 Elsevier Ltd. All rights reserved.

Item Type: Article
Authors (ICR Faculty only): Dowsett, Mitch and Johnston, Stephen and Martin, Lesley-Ann and Smith, Ian
All Authors: Dowsett, M., Martin, L. A., Smith, I., Johnston, S.
Uncontrolled Keywords: aromatase inhibitor; oestrogen receptor; anastrozole; letrozole; resistance Breast-cancer cells; term estrogen deprivation; postmenopausal women; estradiol hypersensitivity; neoadjuvant treatment; receptor; tamoxifen; expression; combination; aib1
Research teams: Clinical Units > Breast Unit
ICR divisions > Breast Cancer Research > Endocrinology
ICR divisions > Molecular Pathology > Endocrinology
Depositing User: EPrints Services
Date Deposited: 10 Aug 2007 20:51
Last Modified: 06 Feb 2014 15:28
URI: http://publications.icr.ac.uk/id/eprint/2168

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