What Is the Blood-Brain Barrier and How Does it Affect Brain Tumor Treatment?

David Reardon, Patrick Wen, brain tumors

Patrick Wen, MD, (left), and David Reardon, MD, of Dana-Farber’s Center for Neuro-Oncology.

The blood-brain barrier surrounds the brain and prevents harmful toxins and bacteria in the blood stream from entering the vital organ. What evolved as a life-saving defense, however, also blocks many drugs from reaching the brain, creating a major problem in treating brain tumors.

The blood-brain barrier is formed by tightly-packed cells lining the walls of vessels in the brain that allow entrance to only a few kinds of molecules, like water, some gases, and essential nutrients.

“We are keenly aware of the potential therapeutic limitations posed by the blood-brain barrier and are actively pursuing strategies to overcome it and enable effective delivery of promising therapeutics into brain tumors,” says David Reardon, MD, clinical director of the Center for Neuro-Oncology.

Fortunately, some chemotherapy agents, including temozolomide, lomustine, and carmustine, can slip through the barrier to attack cancer cells. “Most other chemotherapies and nearly all targeted agents do not pass through,” notes Reardon.

If immunotherapy proves to be an effective treatment for brain tumors, it has the great advantage of not being deterred by the blood-brain barrier. That’s because immunotherapy drugs work by stimulating the patient’s immune system, which consists of cancer-fighting white blood cells that do enter the brain. Research in this area is in early stages, but Reardon says “many exciting new immunotherapy treatments are being evaluated in clinical trials” at Dana-Farber.

Meanwhile, the quest for new drugs that can sneak through the brain’s defensive perimeter continues. It’s not easy to determine how much of a drug is getting to the brain, but scientists at Dana-Farber and Brigham and Women’s Hospital are collaborating on a novel method for assessing the question. It’s a tool based on mass spectrometry that reveals the distribution of a drug in the brain, enabling researchers to focus only on experimental medications that show they can reach their destination. The investigators are working toward the ultimate test in which they would examine samples of a patient’s tumor removed following treatment with a new drug to find out how well it penetrated the tumor and how effectively it killed cancer cells.

Another strategy for drug delivery is to temporarily disrupt the blood-brain barrier long enough for the medication to pass through. One way to do this is to administer radiation, which opens the barrier for a few weeks, Reardon says.

Neuro-oncology researchers are also evaluating other delivery vehicles, such as tiny drug-containing nanoparticles that could smuggle anti-cancer compounds through the barrier.

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