Journal
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
Volume 125, Issue 1-2, Pages 13-22Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jsbmb.2011.02.001
Keywords
Breast cancer; Aromatase inhibitors
Funding
- NCI NIH HHS [R01 CA062483-28, R01 CA062483] Funding Source: Medline
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Estrogens are known to be important in the growth of breast cancers in both pre and postmenopausal women. As the number of breast cancer patients increases with age, the majority of breast cancer patients are postmenopausal women. Although estrogens are no longer made in the ovaries after menopause, peripheral tissues produce sufficient concentrations to stimulate tumor growth. As aromatase catalyzes the final and rate-limiting step in the biosynthesis of estrogen, inhibitors of this enzyme are effective targeted therapy for breast cancer. Three aromatase inhibitors (Als) are now FDA approved and have been shown to be more effective than the antiestrogen tamoxifen and are well tolerated. Als are now a standard treatment for postmenopausal patients. Als are effective in adjuvant and first-line metastatic setting. This review describes the development of Als and their current use in breast cancer. Recent research focuses on elucidating mechanisms of acquired resistance that may develop in some patients with long term AI treatment and also in innate resistance. Preclinical data in resistance models demonstrated that the crosstalk between ER and other signaling pathways particularly MAPK and PI3K/Akt is an important resistant mechanism. Blockade of these other signaling pathways is an attractive strategy to circumvent the resistance to Al therapy in breast cancer. Several clinical trials are ongoing to evaluate the role of these novel targeted therapies to reverse resistance to Als. Article from the special issue on 'Targeted Inhibitors'. (C) 2011 Elsevier Ltd. All rights reserved.
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