Protect bones from metastases

A remedy has been found to combat bone lesions in breast cancer

Anna Stavina, XX2 century

When breast cancer (BC) spreads through the body, it can destroy a patient's healthy bones, causing many problems. Scientists from the Huntsman Cancer Institute at the University of Utah have discovered a new mechanism underlying metastatic bone damage. They also figured out how to block it with a drug. Preliminary test results of the new drug look promising.

The results of the study were published in the publication Science Translational Medicine (Andrade et al., RON kinase: A target for treatment of cancer-induced bone destruction and osteoporosis).

Every year, about 400 thousand people around the world die because breast cancer has spread through the body. Approximately 75% of cases of metastatic breast cancer have bone lesions.

The head of the study, Alana Welm, associate professor of oncology at the University of Utah, explains: "When breast cancer spreads to the bones, it destroys them. The process is similar to the development of osteoporosis, but it is much larger. Cancer eats away at the bone tissue, literally leading to holes in the skeleton."

Patients at the same time suffer from pain and fractures. If metastases have penetrated the spine, the vertebrae may collapse, which will lead to compression of the spinal cord.

To study the process of bone damage, Velm and her colleagues injected tumor cells into the bone tissue of mice. The bones of the experimental animals began to break down, which, in general, is not typical for mice. Then the scientists discovered that some breast cancer cells secrete a protein that stimulates macrophages. This protein was captured by the so-called "RON protein", which caused bone cells to secrete acid that destroys bone tissue.

Having found out the mechanics of the process, the scientists brought out a line of mice that lacked the gene responsible for the synthesis of the RON protein. Thus, they planned to find out what would happen in the absence of a receptor for a protein that stimulates macrophages.

"We found that this protects the bones from decay," says Velm. – The process of destruction has slowed down, perhaps 10 times, almost completely stopped. Even if the tumor cells penetrated into the bone tissue, the mouse bones were preserved much better."

But human genes can't just be "thrown out." Therefore, scientists turned for help to a biotech company that was developing a RON protein inhibitor. The drug was tested on mice – and again the result was positive. The animals were able to move on their own paws for longer and suffered less from fractures.

The company has already started conducting phase I clinical trials. Velm and her colleagues joined this study to study the effect of the drug on human bones. However, since the main purpose of the trials was to assess the safety of the new drug, the number of participants was small. The group included both men and women who suffered from various oncological diseases. None of the participants had metastatic bone lesions. However, almost all of the volunteers were over 50 years old, which means they could develop age-related disorders of bone metabolism. And several women have already begun to progress osteoporosis. The test results were encouraging.

The metabolism (remodeling) of bone tissue is characterized by two opposite processes: the formation of new bone tissue and the resorption (degradation) of the old one. Bone mass depends on the balance between resorption and bone formation at a particular time period. Normally, the amount of new tissue is equivalent to the destroyed one. In all diseases of the skeleton, violations of bone remodeling processes occur, which is accompanied by deviations in the level of biochemical markers.

"We were able to study the blood samples of the study participants before the start of therapy and after 28 or more days of taking the drug. And we have seen how the number of markers of age–related disorders of bone metabolism decreases," explains Velm. – In almost two-thirds of cases, we have seen how the indicators associated with the destruction of bone tissue decrease. And approximately the same number of patients had increased concentrations of markers indicating bone restoration."

In women, the effect was more noticeable, perhaps due to the fact that in the postmenopausal period, bone renewal disorders are more pronounced. After the first month of therapy, 72% of patients had a 25% decrease in bone destruction activity.

The drug was well tolerated, the number of side effects was small. The results of the Phase I tests look encouraging. But now the next step is required – the study of the effectiveness of the new drug directly in breast cancer. Since not all types of breast tumors secrete a protein that stimulates macrophages, scientists plan to focus on patients who have high levels of this protein.

According to the researchers, the protein stimulating macrophages is secreted by breast cancer cells in about 40% of cases. "If we can help 40% of patients with metastatic breast cancer, this is a huge step forward. Even if I see that our work has helped one person, I will be delighted," Velm admits.

The researcher believes that the new drug can work well in combination with already known drugs, especially in patients resistant to existing treatments. She also hopes that the remedy will be effective for other types of cancer affecting bone tissue, and for osteoporosis.

Portal "Eternal youth" http://vechnayamolodost.ru  27.01.2017