Treating Bone Loss in Breast Cancer

A secondary concern of breast cancer is the risk of the cancer cells spreading to the bones, causing severe pain and affecting quality of life. But a new study has identified how bones get damaged and researchers from Huntsman Cancer Institute (HCI) at the University of Utah are developing a new drug to mitigate this problem.

The findings were published in Science Translational Medicine. Alana Welm, PhD, an associate professor of oncological sciences at the University of Utah, led the study.

“When breast cancer spreads to the bones, it causes destruction of the bone,” said Welm. “It’s a similar process to what happens in osteoporosis, except to a much greater extent. The cancer causes bone to be eaten up,” she added, in a news release.  

To test their concept the research team inserted breast cancer cells into mouse bones. The mice experienced large amounts of bone degradation. Welm discovered certain breast cancer cells created a protein called Macrophage Stimulating Protein (MSP). The protein was then taken from the environment by a protein called RON, which causes the bone cells to secrete acids, destroying the bone.

Welm and colleagues then eliminated the mouse gene containing the RON protein. The process protects the bones from destruction, which could be a game-changer for patients, 75% of whom experience bone fractures and degradation.

The next step was to translate this study in human populations. Because it isn't possible to knock out peoples’ genes, the researchers partnered with a biotech company to develop a RON inhibitor-an oral drug that blocks the activity of RON. Welm’s group first tested this drug in mice and again saw positive results. The animals could walk on their legs longer and didn’t experience fractures.

The biotech company conducted a phase I clinical trial to test the RON inhibitor in patients in Australia, so Welm and her group collaborated with them to investigate the effect of the drug on human bones.

The trial was initially created to test the drug's safety, so the study population was limited. It included both men and women with various cancer types. None of them had cancer in the bones at the time the study was conducted. However, most patients were older than 50, which meant they were likely to have age-related bone turnover. Some of the women already had osteoporosis.

After one month of therapy, 72% of women experienced at least a 25% decrease in bone destruction.

“With a biopsy, we can actually look to see if the tumor expresses MSP,” said Welm. “About 40% of breast cancers express MSP in the tumor-so that would be the population we would try to treat with the drug. If we can help 40% of metastatic breast cancer patients, that’s a great step."

Additional studies on a larger population group may demonstrate efficacy for more patients. Welm believes this may lead to treatments for other cancer types as well as noncancerous osteoporosis.