New Research by Israeli Scientists Shows Existing Drugs May Curb Bone Metastasis in Breast Cancer Patients

Research from Tel Aviv University reveals potential breakthrough in treatment, utilizing a novel drug combination to reduce bone metastasis and improve survival rates

While complications are prevalent in cancer patients, many people aren’t aware of just how prevalent they are. More than 75% of metastatic breast cancer patients suffer from bone metastasis. Tel Aviv University researchers Prof. Neta Erez and Dr. Lea Monteran have developed a novel therapeutic strategy to address this often-life-threatening complication. Their breakthrough uses a combination of available drugs to slow bone metastasis progression and enhance survival rates.

Prof. Neta Erez. (Courtesy)

Their findings have been validated in patient samples, affirming the treatment’s potential effectiveness across cancer types. While this study offers great promise for people suffering from bone metastasis, clinical trials are ongoing. Therefore, time is needed before the medication reaches patients.

The Media Line spoke with Erez and Monteran to learn more about their groundbreaking research.

Prof. Erez, who works in Tel Aviv University’s Faculty of Medicine, has been studying cancer from the early stages of her career. She obtained a master’s degree and Ph.D. at the Weizmann Institute in Israel before doing postdoctoral research at the University of California in San Francisco. When she returned to Israel, she opened her lab in the Faculty of Medicine in Tel Aviv and decided its main focus would be understanding the microenvironment and metastasis biology.

According to Erez, this research project was led by a research student in her lab—Monteran. “When we started, she was a Ph.D. student. She developed this model in the lab and then did all the experiments,” Erez said.

“We started with a very broad question and then focused on the role of the interaction between the granulocytes and the T cells. We loved it and just went with it,” added Dr. Monteran, who has long been interested in immunology and cancerology, especially in the tumor microenvironment.

Cancer is one of the main causes of death in the world, so it was always important for me to work on it

“Cancer is one of the main causes of death in the world, so it was always important for me to work on it. I wanted to work on something very big and, hopefully, help a large number of people at some point,” she said.

The focus of the research team was on understanding the biology of metastasis.

“This is very important because most deaths from cancer occur from metastasis to distant organs and not from the primary tumor, especially in breast cancer, where the primary tumor is usually surgically removed,” Erez explained.

Breast cancer frequently metastasizes to the bones causing significant harm. Bone metastasis then leads to osteolytic damage resulting in fractures and pain, even paralysis. Early detection and prompt treatment are crucial to prevent further complications.

However, MRI and CT imaging modalities cannot diagnose early disease.

“When metastases are diagnosed, it’s usually too late, and this is because of our inability to discover micrometastasis,” Erez said, adding that a tumor is like an ecosystem, becoming a multicellular organ where various cells from surrounding tissue get incorporated into it. When in the breast, the primary tumor is surrounded by integrated tissue.

Understanding this is crucial for developing effective treatments, according to Erez.

“Cancer cells manage to go into the bloodstream and spread to the bone. We were trying to understand the early changes in the bone that allow these disseminated breast cancer cells to grow,” she said.

During the study, researchers analyzed genes in immune cells during early- and late-stage metastasis, identifying changes in immune cells.

“We understood that some of them are genes that dictate immune suppression. In other words, they suppress the ability of T lymphocytes to kill the cancer cells,” said Erez.

According to Monteran, “It seems that immunotherapy is not developed in a good way in breast cancer patients. It was interesting to us because it has been the most successful treatment in the cancer field in the past decade. So why isn’t it working on breast cancer? That’s why we started to look at the immune system in bone metastasis,” she said.

Dr. Lea Monteran and Dr. Nour Ershaid, a co-author of the study. (Courtesy)

The researchers conducted a study on chronic inflammatory diseases and devised a combination of two antibiotics. The first is an antibody that inhibits IL-1 beta, a cytokine used to treat these diseases. The second antibiotic is called anti-TGT, an immune checkpoint inhibitor that is currently undergoing clinical trials. Although it’s not yet approved for breast cancer, it shows promise as a potentially effective treatment.

Both researchers used mice throughout the experimental process. “We used a mouse model that is based on injection of breast cancer cells to the mouse mammary gland,” Monteran explained. “Then, these cells develop into a breast tumor. We remove the primary tumor, much as it is done in women, suture, and then we wait. About a month later, the mice developed bone metastasis,” she said.

The main breakthrough here is to combine these two and not just target the immune checkpoint, but also target the immune suppression mediated by the cells that express IL-1 beta cytokine

Her team started treating mice immediately after removing the primary breast tumor. They found that the treated mice had significantly less bone metastasis and lived longer than the control mice that were treated with an irrelevant antibody.

“The fact that we thought of this combination is a very novel thing,” said Erez. “The main breakthrough here is to combine these two and not just target the immune checkpoint, but also target the immune suppression mediated by the cells that express IL-1 beta cytokine. This is the novel pathways and novel interactions that we have discovered and revealed in our study,” she shared.

Monteran added: “In the mice, the PD-1 treatment has severe side effects in 30% of the mice, while PG didn’t show any severe side effects. For us, it was very impressive and promising because one of the main problems of immunotherapy is the side effects of the treatment itself,” she said.

“But these are just mice. The next thing we wanted to do was to know whether these pathways we identified could be relevant to human bone metastasis,” she said.

The researchers found that the same therapy may be effective in treating human patients.

Clinical trials cost a lot of money. I will now try, in collaboration with clinicians, to see if we can get the drug companies to give us the drug for a trial.

This experiment took about six years. The next step is for the study to advance to the clinical trial stage.

(R-L) Prof. Neta Erez and Dr. Lea Monteran. (Courtesy)

“I sincerely hope that this can be taken further. Clinical trials cost a lot of money. I will now try, in collaboration with clinicians, to see if we can get the drug companies to give us the drug for a trial,” Erez said.

“We finished our path as an academic research lab because that’s where we stand. We want to see if we can move things forward with patients. It’s not totally in our hands, but we try,” added Monteran.

Funding for the study was provided by various organizations, including the Israel Cancer Research Fund, the Israel Science Foundation, Worldwide Cancer Research, and the US Department of Defense.