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

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.

Related Stories

HOXB7 gene promotes tamoxifen resistance

Dec 11, 2010

Many postmenopausal women with early-stage breast cancers who initially respond well to tamoxifen become resistant to the drug over time and develop recurrent tumors. Johns Hopkins Kimmel Cancer Center researchers have found ...

Recommended for you

Researcher to cancer: 'Resistance will be futile'

6 hours ago

Turning the tables, Katherine Borden at the University of Montreal's Institute for Research in Immunology and Cancer (IRIC) has evoked Star Trek's Borg in her fight against the disease. "Cancer cells rapidly ...

How does prostate cancer form?

8 hours ago

Prostate cancer affects more than 23,000 men this year in the USA however the individual genes that initiate prostate cancer formation are poorly understood. Finding an enzyme that regulates this process ...

Low risk of malignancy for small complex adnexal masses

15 hours ago

(HealthDay)—For older women with small complex adnexal masses, the overall risk of malignancy is low, according to a study published in the December issue of the American Journal of Obstetrics & Gynecology.

User 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.