Early Research Uncovers a Strategy That Helps Brain Mets Survive

Researchers have uncovered a new strategy that breast cancer brain metastases (brain mets) use to supercharge growth and avoid death. When this strategy was blocked in lab studies, cancer cells died off, raising the possibility of a new treatment approach for brain mets. 

The study is part of a growing research field focused on understanding how tumors survive in the brain, “so we can figure out how to kill that tumor,” says Mauricio Reginato, PhD, a cancer biology professor at Drexel University and author of this new study. Brain mets affect 10–15% of people with metastatic breast cancer and are known to be especially  difficult to treat because the brain is protected by something called the blood brain barrier, which is a layer of cells that keeps toxins out.  

So how do brain mets survive in the brain? They make some crafty adaptations. The brain is like a desert for brain mets, says Reginato. It lacks the basic nutrients tumors need to survive. Glucose, the nutrient tumors usually feed off in the breast, isn’t available to them in the brain. The brain sucks up glucose to power the many important processes that keep us alive. 

So in order to survive, brain mets ditch their normal diet for another energy source — a fatty acid called acetate. Reginato’s research has focused on understanding how brain mets use acetate, in hopes of finding a drug that could cut off this new source of food. 

His new study showed that brain mets change acetate into a compound that helps tumors grow, like turning a banana into a protein-packed, pre-workout smoothie. This cellular-energy smoothie also shields tumors from a process that kills off their cells. Other brain tumors have been shown to do this, but this study is the first to show this strategy in brain mets. 

When Reginato used an experimental drug to turn off the protective shield and reactivate the cell-death process, cancer cells died off and tumor growth slowed. Next, he plans to study if this experimental drug could work in combination with radiation or immunotherapy. By weakening the protective shield around these tumors, he thinks the cancer may be more vulnerable to other therapies. “I’m very hopeful,” he says.

The experiments were done in cells and mice that mimic how the human brain looks with triple-negative breast cancer metastases. It’s too early to say how the drug will work in humans, but the study accomplished a critical first step in developing a potential cancer drug: it identified a target.  Plus, Reginato’s experimental drug can get into the brain, a key quality needed in any brain drug.

“We can only take [the drug] so far as basic scientists,” he says, “so we’re hoping we can license this drug to somebody that’s interested in developing it.”