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Potential New Therapeutic Target for Brain Metastases from Breast Cancer

Metastatic breast cancer (also called stage IV) is breast cancer that has spread to another part of the body, most commonly the liver, brain, bones, or lungs. There are many treatment options that are available for metastatic breast cancer including surgery, chemotherapy, radiation therapy, and now there may be a new treatment that will offer hope. Researchers led by CU Cancer Center member Diana Cittelly, PhD, report a potential new treatment option for breast cancer that spreads to the brain.

Their findings are published in the journal Clinical Cancer Research, in a paper titled, “IL13Rα2 promotes proliferation and outgrowth of breast cancer brain metastases.”

The researchers investigated the role of interleukin 13 receptor alpha 2 (IL13Ra2), a protein that is found in increased rates in cancer cells that metastasize to other locations in the body.

“We found that patients expressing high levels of IL13Ra2 in their brain metastases have worse survival than those expressing low levels of IL13Ra2, but we could not see this correlation when examining the primary tumors. That was important because it suggested that there is an adaptation of the cancer cells when they spread to the brain, and we could eventually target it,” Cittelly said. “We were able to identify a role for this receptor as a tool in promoting the proliferation and outgrowth of metastasis in the brain.”

According to the study, the survival of women with brain metastases from breast cancer remains very poor with over 80% dying within a year of their diagnosis. The researchers identified IL13Ra2 as a target, with its known vulnerability to CAR T-cell treatment in clinical trials on brain tumors.

“We know that in breast cancer, particularly, there is an increased risk of brain metastasis in younger women, as well as those that have HER-2 positive breast cancers, or a subset of triple-negative breast cancer,” Cittelly said. “We still don’t know exactly what subpopulations of cancer cells can actually grow in the brain, but our studies specifically suggest that there are some interactions with the brain that lead to the upregulation of the IL13Ra2 receptor as a tool to promote the proliferation in that environment.”

The researchers are looking forward to collaborating with CAR T-cell experts to investigate how CAR T-cell therapy can be targeted to IL13Ra2.

“Patients with brain metastases are often considered terminal, and they are excluded from the majority of clinical trials,” she said. “Having something that could be used for that very specific population will be great.

“Then, in the clinical scenario, when people are already presenting with a brain metastasis, we could potentially target IL13Ra2 to decrease the outgrowth of those metastases and decrease the progression,” she said. “If we can target that protein, we can improve the outcomes of these patients.”

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