A study from the University of Michigan Health Rogel Cancer Center has found that combining a fatty acid inhibitor with chemotherapy could enhance treatment for patients with brain metastases from triple-negative breast cancer.
These promising results were published in npj Breast Cancer.
The brain is a challenging environment for cancer cells because it has very few available lipids, which are essential for the cells’ survival.
This forces cancer cells to produce their own lipids. Dr. Nathan Merrill, the study’s lead author and an assistant professor of hematology/oncology at Michigan Medicine, explained that the research aimed to exploit this weakness by inhibiting fatty acid synthase, an enzyme responsible for making fatty acids, in models of triple-negative breast cancer that had spread to the brain.
The study not only showed that combining fatty acid synthase inhibitors with chemotherapy improved treatment effectiveness, but it also revealed that using these inhibitors alone, even at low doses, reduced the cancer cells’ ability to move and spread throughout the body.
Triple-negative breast cancer and HER2-positive breast cancer are known for their high risk of metastasizing to the brain.
To test the combination of fatty acid synthase inhibitors and chemotherapy, Merrill and his team looked for “synergy,” which means evaluating if the two drugs work better together than separately.
Merrill highlighted a significant aspect of their work: the development of two new cell lines from a patient with brain metastases. These cell lines are unique because they came from the same patient and represent multiple resections of the tumor, providing a valuable resource for further research.
The team’s next step is to understand precisely how fatty acid synthase inhibition affects metastases.
Merrill’s lab has developed a device that mimics the brain environment, which they plan to use to identify which stages of the metastatic process are most affected by inhibiting fatty acid synthase. They also plan to test their findings in mouse models.
Fatty acid synthase inhibitors have already been shown to be safe in phase 1 clinical trials and are used in treating non-cancer conditions like metabolic dysfunction-associated steatotic liver disease. These inhibitors are also being evaluated as an add-on therapy for HER2-positive advanced breast cancers.
Although more research is needed, Merrill is hopeful that, with validation in mouse models, these findings could lead to improved treatments for patients with triple-negative breast cancer.
This study provides a new avenue for potentially more effective therapies for a particularly aggressive form of cancer.
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The research findings can be found in npj Breast Cancer.
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