Abigail Klein Leichman

Researchers have developed a new therapeutic strategy of combining two existing medications to inhibit bone metastasis and improve survival in breast cancer patients. They used both an animal model and tissue samples from patients in Israel and the United States.

Based on their findings, the researchers predict that in the future the treatment can be applied to human patients with breast cancer, as well as other types of cancer.

The groundbreaking study was led by Prof. Neta Erez and Dr. Lea Monteran at Prof. Erez’s Laboratory for Tumor Biology at Tel Aviv University’s Faculty of Medical and Health Sciences. The paper was published in Cancer Discovery.

The researchers explain that over 75% of patients with metastatic breast cancer suffer from bone metastases, which destroy bone tissues, causing fractures and pain. Diagnosis of bone metastasis usually occurs 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,” said Erez. “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, etc. 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.”

The researchers found that when bone metastasis begins, T cells from the immune system penetrate the metastases but cannot destroy them because the T cells are inhibited by another type of immune cells. They identified the proteins responsible for this effect, and created a novel therapeutic combination that had never been tried before in order to neutralize these inhibitory proteins and reactivate the T-cells.

When the drug combo was administered to model mice, the bone metastases were reduced, and survival was significantly improved compared to untreated model mice.

Finally, the TAU research team collaborated with the Sheba and Tel Aviv medical centers in Israel 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,” said Erez.

“The great advantage of our strategy is that both drugs are already available on the market, and consequently 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.

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