Study Shows Potential New Treatment Target for Breast Cancer Tumors That Spread to the Brain

Breast cancer cells that spread to the brain need to boost the production of fatty acids, the building blocks of fat, in order to survive there, according to a new study published in Nature Cancer. The discovery points to a novel treatment target for shrinking brain tumors that arise secondary to breast cancer, according to the study authors.

Although therapies that target human epidermal growth factor receptor 2 (HER2) have transformed treatment for patients with breast cancer whose tumor cells express HER2, brain metastases from the disease are typically fatal due to a resistance to anti-cancer therapies effective elsewhere in the body, according to the study. This is due, in part, to the blood-brain barrier that protects the brain against toxins and pathogens in the circulatory system. However, it may also be due to changes in the cancer cells once they reach the brain, including alterations to what and how they metabolize to support tumor survival and growth, according to the study.

The researchers assessed how metabolism differs between breast tumors that traveled to the brain and those that travelled elsewhere in the body, designing experiments in mice. They found that access to fats is limited for breast tumors in the brain. In response, fatty acid synthesis is elevated in the tumor cells through the increased activity of an enzyme called fatty acid synthase.

According to the study authors, the findings demonstrate that when a cancer has spread to a particular organ, potential treatment strategies could take advantage of the nutrient availability at that site. Inhibiting the cancer cells' ability to use that nutrient could potentially lead to their demise. The team notes that an inhibitor of fatty acid synthase, called TVB2166, is currently being evaluated in patients with metastatic breast cancer.

"This compound is not brain-permeable, however, and patients with symptomatic brain metastases are excluded from these trials," said co-corresponding author Matthew Vander Heiden, MD, PhD, an associate director of the Koch Institute at MIT and a member of the Broad Institute of MIT and Harvard, in the press release. "Therefore, the efficacy and safety of this strategy in patients with brain metastases remains to be explored using brain-penetrable fatty acid synthase inhibitors."

REFERENCE

Potential new treatment strategy for breast cancer cells that have spread to the brain [news release]. April 1, 2021. Accessed April 7, 2021. https://www.eurekalert.org/pub_releases/2021-04/mgh-pnt033121.php