A drug approved in Europe to treat osteoporosis（骨质疏松症） has now been shown to stop the growth of breast cancer cells, even in cancers that have become resistant¹ to current targeted therapies, according to a Duke Cancer Institute study. The findings, presented June 15, 2013, at the annual Endocrine Society meeting in San Francisco, indicate that the drug bazedoxifene packs a powerful one-two punch that not only prevents estrogen（雌性激素） from fueling breast cancer cell growth, but also flags the estrogen receptor for destruction.

 

"We found bazedoxifene binds² to the estrogen receptor and interferes³ with its activity, but the surprising thing we then found was that it also degrades the receptor; it gets rid of it," said senior author Donald McDonnell, PhD, chair of Duke's Department of Pharmacology and Cancer Biology.

 

In animal and cell culture studies, the drug inhibited⁴ growth both in estrogen-dependent breast cancer cells and in cells that had developed resistance to the anti-estrogen tamoxifen and/or to the aromatase inhibitors, two of the most widely used types of drugs to prevent and treat estrogen-dependent breast cancer. Currently, if breast cancer cells develop resistance to these therapies, patients are usually treated with toxic⁵ chemotherapy agents that have significant side effects.

 

Bazedoxifene is a pill that, like tamoxifen, belongs to a class of drugs known as specific estrogen receptor modulators (SERMs). These drugs are distinguished⁶ by their ability to behave like estrogen in some tissues, while significantly blocking estrogen action in other tissues. But unlike tamoxifen, bazedoxifene has some of the properties of a newer group of drugs, known as selective estrogen receptor degraders, or SERDs, which can target the estrogen receptor for destruction.

 

"Because the drug is removing the estrogen receptor as a target by degradation⁷, it is less likely the cancer cell can develop a resistance mechanism⁸ because you are removing the target," said lead author Suzanne Wardell, PhD, a research scientist working in McDonnell's lab.

 

Many investigators⁹ had assumed that once breast cancer cells developed resistance to tamoxifen（三苯氧胺）, they would be resistant to all drugs that target the estrogen receptor, McDonnell explained.

 

"We discovered that the estrogen receptor is still a good target, even after it resistance to tamoxifen has developed," he said.

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