Osteoporosis drug stops breast cancer growth, even in resistant tumors
Researchers announced a groundbreaking discovery today: a drug approved in Europe to treat osteoporosis has now been shown to stop the growth of breast cancer cells, even in resistant tumors, according to a Duke Cancer Institute study.
The findings were presented June 15 at the annual Endocrine Society meeting in San Francisco, and revealed that the drug bazedoxifene not only prevents estrogen from stimulating breast cancer cell growth, but it 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 study author Donald McDonnell, PhD, Chairman of Duke's Department of Pharmacology and Cancer Biology.
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 aromatase inhibitors – two of the most widely used drugs used to prevent and treat estrogen-dependent breast cancer. Currently, patients with resistant breast tumors are treated with toxic chemotherapy agents, which have major side effects.
So what is bazedoxifene? Like tamoxifen, it’s a pill that belongs to a class of drugs called specific estrogen receptor modulators (SERMs). These drugs are well-known for their ability to behave like estrogen in some tissues, while significantly blocking estrogen action in other tissues. Unlike tamoxifen, however, bazedoxifene also has some properties of a newer group of drugs called 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 and research scientist Suzanne Wardell, PhD, who works in McDonnell’s lab.
According to McDonnell, many researchers had assumed that once breast cancer cells developed resistance to tamoxifen, they would be resistant to all drugs that target the estrogen receptor.
"We discovered that the estrogen receptor is still a good target, even after it resistance to tamoxifen has developed," he explained.
For the study, researchers tested a variety of breast cancer cell types, including tamoxifen-sensitive cells that developed resistance to the drug lapatinib, which is another targeted treatment used in patients with advanced breast cancer tumors that contain the mutant HER2 gene. These cells had previously been found to reactivate estrogen signaling in order to become drug resistant. In this kind of cell, bazedoxifene also powerfully inhibited cell growth.
In bone tissue, however, bazedoxifene paradoxically mimics the action of estrogen, which helps protect it from destruction.
The good news is that bazedoxifene has already undergone safety and efficacy studies as a treatment for osteoporosis. Wardell therefore says that it should not take long to become a viable option that’s available to patients with advanced breast cancer that has become resistant to other treatment options.
Meanwhile, clinical trials found that the most often reported side effect with bazedoxifene was hot flashes.
SOURCE: Duke Medicine (2013, June 15). Osteoporosis drug stops growth of breast cancer cells, even in resistant tumors, study suggests.