Researchers at Tel Aviv University (TAU) have developed a new therapeutic strategy based on existing medications to inhibit bone metastasis in breast cancer patients.

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

The groundbreaking study was led by Professor Neta Erez and Dr. Lea Monteran at Professor Erez’s Laboratory for Tumor Biology at the Pathology Department of TAU’s Faculty of Medical and Health Sciences. The paper was published on March 1, 2024, in Cancer Discovery.

Over 75% of patients with metastatic breast cancer suffer from bone metastases which destroy bone tissues, causing fractures and a great deal of pain. Moreover, with today’s technologies such as MRI or CT imaging, diagnosis of bone metastasis occurs, in most cases, when the disease cannot be cured. In this study, the researchers looked for a novel way to inhibit the progression of bone metastasis.

“A tumor is more than a collection of cancer cells,” Professor Erez explains. “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, and blood vessels. Moreover, 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.”

To understand the processes 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.

The researchers discovered that the killing activity of T-cells is inhibited by another type of immune cells and 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 been tried before: a drug that counters the activity of the immune-inhibiting cells, along with an antibody that activates T-cells. This combination was administered to mice, and the results were encouraging: the bone metastases were reduced, and survival was significantly improved compared to untreated mice.

In the final stage of the study, the TAU research team collaborated with the Sheba and Ichilov (Tel Aviv) Medical Centers and the Baylor College of Medicine in Texas. They examined tissue samples from bone metastases taken from patients with breast cancer, as well as 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,” Professor Erez says. “The great advantage of our strategy is that both drugs for these activities 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.”

The study was funded by the Israel Cancer Research Fund, the Israel Science Foundation, Worldwide Cancer Research, and the US Department of Defense.