Nav: Home

Huntsman scientists identify bone degradation process within metastatic breast cancer

January 25, 2017

SALT LAKE CITY - Once breast cancer spreads through the body, it can degrade a patient's healthy bones, causing numerous problems. Scientists at Huntsman Cancer Institute (HCI) at the University of Utah have identified a new way that bones get destroyed through cancer. And they've also learned how to block that destruction with a new drug. Initial tests with patients show promising results.

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

Forty-thousand people die every year of breast cancer because the disease has spread to other sites in the body. And approximately 75 percent of the time, it spreads to their bones.

Welm explains, "When breast cancer spreads to the bones, it causes destruction of the bone. It's a similar process to what happens in osteoporosis, except to a much greater extent. The cancer causes bone to be eaten up. So you quite literally get holes in the skeleton."

Patients often suffer from pain and fractures. If the cancer spreads to the spine, the vertebrae can collapse, causing spinal cord compression.

Studying the process, Welm and her colleagues inserted breast cancer cells into mouse bones. The mice experienced large amounts of bone degradation, a rarity in mice. Welm discovered certain breast cancer cells were creating a protein called Macrophage Stimulating Protein (MSP). The MSP was then taken from the environment by another protein called Ron, which causes the bone cells to secrete acids, destroying the bone.

After uncovering the process, the scientists knocked out the mouse gene containing the Ron protein, wanting to see what would happen if the receptor was eliminated.

"We found it completely protected the bones from destruction," says Welm. "We saw probably 10 times less bone destruction, almost down to nothing. Even when the mice got cancer in their bones, the bones stayed in much better shape."

But it isn't possible to simply knock out peoples' genes. So to test the process in humans, HCI scientists worked with a biotechnology company that was developing 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 was conducting a Phase 1 clinical trial to test the Ron inhibitor in cancer patients in Australia, so Welm and her group collaborated with them to investigate the effect of the drug on human bones. Because the trial was initially created to test the safety of the drug, the study was limited. It included both men and women with various types of cancers. None of them had cancer in the bones. But almost all patients were over age 50, which meant they were likely to have age-related bone turnover. And some of the women were starting to get osteoporosis. The data showed encouraging results.

"We were able to look in the blood of those patients before and after they had been treated with the drug for at least 28 days, and we observed less indication of bone turnover," says Welm. "Just under two-thirds had a drop in a marker that monitors bone destruction - and the same amount showed an increase in their bone repair marker."

A larger effect was seen in women, likely because they were post-menopausal with more bone turnover. After just one month of therapy, 72 percent of women saw at least a 25 percent drop in bone destruction - an amount considered effective.

The drug was also well-tolerated in patients, with few side effects. The results look hopeful, but the next step will be testing the drug specifically in breast cancer patients. Since not all breast tumors secrete MSP, researchers will gear clinical trials to patients who exhibit high levels of the protein.

"With a biopsy, we can actually look to see if the tumor expresses MSP," Welm explains. "About 40 percent 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 percent of metastatic breast cancer patients, that's a great step. If we could actually see our work benefit even one person, I would be thrilled."

Welm thinks the drug might work well in combination with existing drug therapies to improve outcomes for patients, especially those whose disease is resistant to current treatments. She also believes the drug could potentially be used for patients with other types of cancer that degrade bones, or for non-cancer-related osteoporosis.
This study was funded by the National Institutes of Health/National Cancer Institute P30 CA042014, R01 CA166422; Department of Defense Breast Cancer Research Program W81XWH-08-1-0109; the Susan G. Komen Foundation; and the Huntsman Cancer Foundation.

About Huntsman Cancer Institute at the University of Utah:

Huntsman Cancer Institute (HCI) is one of the world's top academic research and cancer treatment centers. HCI manages the Utah Population Database - the largest genetic database in the world, with more than 16 million records linked to genealogies, health records, and vital statistics. Using this data, HCI researchers have identified cancer-causing genes, including the genes responsible for melanoma, colon and breast cancer. HCI is a member of the National Comprehensive Cancer Network (a 27-member alliance of the world's leading cancer centers) and is a National Cancer Institute-Designated Comprehensive Cancer Center. HCI treats patients with all forms of cancer and operates several high-risk clinics that focus on melanoma and breast, colon, and pancreas cancers. The HCI Cancer Learning Center for patient and public education contains one of the nation's largest collections of cancer-related publications. The institute is named after Jon M. Huntsman, a Utah philanthropist, industrialist, and cancer survivor.

University of Utah Health Sciences

Related Breast Cancer Articles:

Partial breast irradiation effective treatment option for low-risk breast cancer
Partial breast irradiation produces similar long-term survival rates and risk for recurrence compared with whole breast irradiation for many women with low-risk, early stage breast cancer, according to new clinical data from a national clinical trial involving researchers from The Ohio State University Comprehensive Cancer Center - Arthur G.
Breast screening linked to 60 per cent lower risk of breast cancer death in first 10 years
Women who take part in breast screening have a significantly greater benefit from treatments than those who are not screened, according to a study of more than 50,000 women.
More clues revealed in link between normal breast changes and invasive breast cancer
A research team, led by investigators from Georgetown Lombardi Comprehensive Cancer Center, details how a natural and dramatic process -- changes in mammary glands to accommodate breastfeeding -- uses a molecular process believed to contribute to survival of pre-malignant breast cells.
Breast tissue tumor suppressor PTEN: A potential Achilles heel for breast cancer cells
A highly collaborative team of researchers at the Medical University of South Carolina and Ohio State University report in Nature Communications that they have identified a novel pathway for connective tissue PTEN in breast cancer cell response to radiotherapy.
Computers equal radiologists in assessing breast density and associated breast cancer risk
Automated breast-density evaluation was just as accurate in predicting women's risk of breast cancer, found and not found by mammography, as subjective evaluation done by radiologists, in a study led by researchers at UC San Francisco and Mayo Clinic.
More Breast Cancer News and Breast Cancer Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Erasing The Stigma
Many of us either cope with mental illness or know someone who does. But we still have a hard time talking about it. This hour, TED speakers explore ways to push past — and even erase — the stigma. Guests include musician and comedian Jordan Raskopoulos, neuroscientist and psychiatrist Thomas Insel, psychiatrist Dixon Chibanda, anxiety and depression researcher Olivia Remes, and entrepreneur Sangu Delle.
Now Playing: Science for the People

#537 Science Journalism, Hold the Hype
Everyone's seen a piece of science getting over-exaggerated in the media. Most people would be quick to blame journalists and big media for getting in wrong. In many cases, you'd be right. But there's other sources of hype in science journalism. and one of them can be found in the humble, and little-known press release. We're talking with Chris Chambers about doing science about science journalism, and where the hype creeps in. Related links: The association between exaggeration in health related science news and academic press releases: retrospective observational study Claims of causality in health news: a randomised trial This...