雌激素受体
生物
雌激素受体α
雌激素
芳香化酶
内科学
癌症研究
雌激素受体
乳腺癌
富维斯特朗
内分泌学
三苯氧胺
癌症
医学
作者
Nicole A. Traphagen,Sarah R. Hosford,Amanda Jiang,Jonathan D. Marotti,Brooke L. Brauer,Eugene Demidenko,Todd W. Miller
出处
期刊:Oncogene
[Springer Nature]
日期:2021-04-19
卷期号:40 (19): 3408-3421
被引量:11
标识
DOI:10.1038/s41388-021-01782-w
摘要
Estrogen receptor alpha (ER)-positive breast cancer is commonly treated with endocrine therapies, including antiestrogens that bind and inhibit ER activity, and aromatase inhibitors that suppress estrogen biosynthesis to inhibit estrogen-dependent ER activity. Paradoxically, treatment with estrogens such as 17b-estradiol can also be effective against ER+ breast cancer. Despite the known efficacy of estrogen therapy, the lack of a predictive biomarker of response and understanding of the mechanism of action have contributed to its limited clinical use. Herein, we demonstrate that ER overexpression confers resistance to estrogen deprivation through ER activation in human ER+ breast cancer cells and xenografts grown in mice. However, ER overexpression and the associated high levels of ER transcriptional activation converted 17b-estradiol from a growth-promoter to a growth-suppressor, offering a targetable therapeutic vulnerability and a potential means of identifying patients likely to benefit from estrogen therapy. Since ER+ breast cancer cells and tumors ultimately developed resistance to continuous estrogen deprivation or continuous 17b-estradiol treatment, we tested schedules of alternating treatments. Oscillation of ER activity through cycling of 17b-estradiol and estrogen deprivation provided long-term control of patient-derived xenografts, offering a novel endocrine-only strategy to manage ER+ breast cancer.
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