Osteoporosis drug stops growth of breast cancer cells, even in resistant tumors

June 15, 2013

A drug approved in Europe to treat osteoporosis has now been shown to stop the growth of breast cancer cells, even in cancers that have become resistant 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 from fueling breast , but also flags the estrogen receptor for destruction.

"We found bazedoxifene binds to the estrogen receptor and interferes 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 .

In animal and cell culture studies, the drug inhibited growth both in estrogen-dependent breast cancer cells and in cells that had developed resistance to the anti-estrogen tamoxifen and/or to the , 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 toxic 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 distinguished 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 degradation, it is less likely the cancer cell can develop a resistance mechanism because you are removing the target," said lead author Suzanne Wardell, PhD, a research scientist working in McDonnell's lab.

Many investigators had assumed that once developed resistance to tamoxifen, 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.

The investigators tested a variety of breast cancer cell types, including -sensitive cells that are resistant to the drug lapatinib, another targeted therapy that is used to treat patients with advanced breast cancer whose tumors contain the mutant HER2 gene. These cells had previously been shown to reactivate estrogen signaling in order to acquire drug resistance. In this cell type, bazedoxifene also potently inhibited cell growth.

Paradoxically, in bone tissue, bazedoxifene mimics the action of estrogen, helping protect it from destruction. Because bazedoxifene has already undergone safety and efficacy studies as a treatment for , it may be a viable near-term option for patients with advanced whose tumors have become resistant to other treatment options, Wardell reported. In clinical trials, the most often reported side effect was hot flashes in the bazedoxifene treatment groups.

Explore further: Studies show increasing evidence that androgen drives breast cancer

Related Stories

Studies show increasing evidence that androgen drives breast cancer

April 10, 2013
Estrogen and progesterone receptors, and the gene HER2 – these are the big three markers and/or targets in breast cancer. Evidence presented at the AACR Annual Meeting 2013 adds a fourth: androgen receptors.

New finding gives clues for overcoming tamoxifen-resistant breast cancer

November 2, 2012
(Medical Xpress)—A University of Cincinnati (UC) cancer biology team reports breakthrough findings about specific cellular mechanisms that may help overcome endocrine (hormone) therapy-resistance in patients with estrogen-positive ...

Researchers identify new pathway, enhancing tamoxifen to tame aggressive breast cancer

April 23, 2013
Tamoxifen is a time-honored breast cancer drug used to treat millions of women with early-stage and less-aggressive disease, and now a University of Rochester Medical Center team has shown how to exploit tamoxifen's secondary ...

Spread of breast cancer linked to kisspeptins which normally inhibit metastasis

April 16, 2013
KISS 1 is a metastasis-suppressor gene which helps to prevent the spread of cancers, including melanoma, pancreatic and ovarian cancers to name a few. But new research from Western University's Schulich School of Medicine ...

Recommended for you

Vitamin C may encourage blood cancer stem cells to die

August 17, 2017
Vitamin C may "tell" faulty stem cells in the bone marrow to mature and die normally, instead of multiplying to cause blood cancers. This is the finding of a study led by researchers from Perlmutter Cancer Center at NYU Langone ...

Outdoor light at night linked with increased breast cancer risk in women

August 17, 2017
Women who live in areas with higher levels of outdoor light at night may be at higher risk for breast cancer than those living in areas with lower levels, according to a large long-term study from Harvard T.H. Chan School ...

Scientists develop novel immunotherapy technology for prostate cancer

August 17, 2017
A study led by scientists at The Wistar Institute describes a novel immunotherapeutic strategy for the treatment of cancer based on the use of synthetic DNA to directly encode protective antibodies against a cancer specific ...

Toxic formaldehyde is produced inside our own cells, scientists discover

August 16, 2017
New research has revealed that some of the toxin formaldehyde in our bodies does not come from our environment - it is a by-product of an essential reaction inside our own cells. This could provide new targets for developing ...

Cell cycle-blocking drugs can shrink tumors by enlisting immune system in attack on cancer

August 16, 2017
In the brief time that drugs known as CDK4/6 inhibitors have been approved for the treatment of metastatic breast cancer, doctors have made a startling observation: in certain patients, the drugs—designed to halt cancer ...

Researchers find 'switch' that turns on immune cells' tumor-killing ability

August 16, 2017
Molecular biologists led by Leonid Pobezinsky and his wife and research collaborator Elena Pobezinskaya at the University of Massachusetts Amherst have published results that for the first time show how a microRNA molecule ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.