Israeli researchers reach bone metastasis breakthrough for breast cancer patients

Tel Aviv University (TAU) researchers have developed a new therapeutic strategy based on existing medications to inhibit bone metastasis in breast cancer patients. When a patient has this malignancy and it isn’t stopped from spreading, most often – in 75% of cases – it spreads to the bone, destroying its tissues and causing fractures and a great deal of pain.

Using both an animal model and tissue samples from patients in Israel and the US, the researchers showed that a combination of drugs already available on the market can hinder bone metastasis and improve survival. Based on their findings, they predict that in the future, the treatment will be applied to human patients with breast cancer as well as other types of cancer.

In this groundbreaking study, the researchers looked for a novel way to inhibit the progression of bone metastasis. The study was led by Prof. Neta Erez and Dr. Lea Monteran at Erez’s Laboratory for Tumor Biology at the pathology department of the university’s Faculty of Medical and Health Sciences. The paper has just been published in the journal Cancer Discovery under the title “Clofazimine Reduces Side Effects from Dual Immune Checkpoint Blockade.”

With today’s technologies, such as MRI and CT imaging, a diagnosis of bone metastasis mostly occurs when the disease has already gone too far and the patient can no longer be cured.

“A tumor is more than a collection of cancer cells. Just like healthy tissues, a tumor is a whole ecosystem consisting of reciprocal interactions between different cell types, including cells of the immune system, connective tissues, blood vessels, and more.

Cancer cells often ‘corrupt’ normal cells, causing them to ‘collaborate’ with the tumor and support the growth of cancer cells.

Blocking the communication channels between cancer cells and healthy cells at an early stage can hinder the growth of cancer cells in the bones. To achieve this, the early stages of the process must be investigated,” Erez explained.

Novel approach to combatting bone metastasis

To understand the process of bone metastasis, the researchers compared three types of bones from model mice – healthy, early-stage metastasis, and advanced metastasis. They found that when bone metastasis begins, T cells from the immune system arrive on the scene and penetrate the metastases but are unable to destroy them.

Next, the researchers discovered that another type of immune cell inhibits the killing activity of T cells, and they identified the proteins responsible for this effect. To neutralize these inhibitory proteins and reactivate the T-cells, they created a novel therapeutic combination that had never before been tried – a drug that counters the activity of the immune-inhibiting cells along with an antibody that activates T cells. This combination was administered to model mice, and the results were encouraging. The bone metastases were reduced, and survival was significantly improved compared to untreated model mice, the authors wrote.

At the final stage of the study, the TAU research team collaborated with Tel Aviv Sourasky Medical Center, Sheba Medical Center at Tel Hashomer, and the Baylor College of Medicine in Texas. They examined tissue samples from bone metastases taken from patients with breast and other types of cancer and found that the immune cells inhibiting T cells express the same proteins as those found in the animal model.

“Our findings suggest that the combined treatment – attacking the cells that inhibit T cells while activating the T cells – can be effective for treating bone metastasis resulting from breast cancer as well as other types of cancer,” Erez concluded. “The great advantage of our strategy is that both drugs are already available on the market, so the process of obtaining permits to use them against bone metastasis in humans can be relatively short. At the same time, clinical trials are needed to verify the effectiveness of the new therapeutic strategy.”