Under the Microscope: A Window into Brain Metastasis

Although patients with breast cancer are living longer thanks to new therapies and better detection, many of them go on to face a serious secondary cancer, or metastasis, in the brain. Depending on the breast cancer subtype, survivors can face up to a 50% chance of developing brain metastases.

“Brain metastasis is especially common for breast cancer, but it also occurs for some lung, colon and skin cancers,” said Qing Chen, M.D., Ph.D., assistant professor at The Wistar Institute in Philadelphia. “Unfortunately, the cancer therapies we have right now don’t work for tumors in the brain.”

Much of today’s research into fighting brain metastases focuses on finding drugs that directly kill cancer cells. With V Foundation support, Chen and her colleagues are taking a different approach. They believe taking an up-close look at the process by which cancer cells from other parts of the body settle in the brain and begin to grow there could help point the way to game-changing new therapies.

“We want to figure out how the cancer cells get support from their surroundings in the brain, a microenvironment that is unique and constantly changing,” said Chen. “Once we understand that, we can find ways to cut off this interaction and stop the cancer from growing.”

Watching cancer grow

To understand the extremely complex molecular environment in the brain, Chen and her colleagues are using an advanced microscopy technique to directly observe metastasis growth in the brains of living mice.

A brain imaging technique, originally developed in neurobiology studies, is used to visualize glowing chemicals to track the movement of particular cells and molecules in the brain.

“In this way, we can track the activation of a molecular pathway in the same brain metastatic lesions over time,” said Chen. “This lets us see the exact stage at which a specific pathway influences metastasis.”

A new molecular pathway

The researchers have discovered cancer cells that travel to the brain interact with star-shaped brain cells aptly called astrocytes. This interaction causes the cancer cells to emit signals through a mechanism known as the interferon signaling pathway, which is involved in cell growth.

“By imaging the molecules involved in this pathway, we saw that interferon signaling is switched on very soon after cancer enters the brain and then remains on as the tumor begins to grow,” said Chen. “These findings tell us that therapies targeting this signaling pathway would need to be administered very early and continued as the brain metastasis progresses.”

The researchers are also using the imaging approach to better understand how the unique microenvironment of the brain affects the delivery of cancer drugs. Watching drug delivery directly could offer important insights into the best timing for delivery or whether it is better to deliver drugs to the edge of the brain tumor or the center of the brain mass, for example.

“The V Foundation funding allowed us to build a team, get a very technical imaging setup working properly and figure out the best protocols for studying brain metastasis,” said Chen. “Because they were willing to take on risky projects like ours, we were able to gather enough data to get NIH funding to continue this research.”