What is the blood-brain barrier, and how can we get past it to treat cancer?

One of the most significant challenges for treating brain cancers is the blood-brain barrier, which protects the brain but also prevents certain drugs and therapies from getting through to where they are needed.

UT MD Anderson researchers are exploring methods to better deliver medications across the blood-brain barrier to treat patients with cancers of the brain and nervous system.

Here’s what to know about the blood-brain barrier and new advances in overcoming it to treat cancer.

What is the blood-brain barrier?

The blood-brain barrier is a natural protective membrane. Think of it like a series of garage doors tightly packed together along blood vessels in the central nervous system (CNS), strictly controlling what goes in to reach the brain and what stays out.

It has the ability to control which substances pass through, shielding the brain against potentially harmful substances such as pathogens and toxins. However, it can also prevent potentially life-saving medications such as immunotherapy and chemotherapy from reaching brain tumors, making treatment difficult and inefficient.

Neurosurgery researcher Joseph McCarty, Ph.D., focuses much of his work on studying the biology of the neurovascular system in depth in order to find ways to understand how the different cells communicate. Knowing how the blood-brain barrier is normally formed in a healthy brain can help when looking at tumor and stroke models.

“We want to be very precise in the way we open the blood-brain barrier, which involves a combination of understanding how it usually forms and how it’s regulated in a healthy brain, and then also how it works in tumors or stroke models,” says McCarty.

What are some ways to open the gates of the blood-brain barrier?

UT MD Anderson scientists and clinicians are working to hack the remote for the blood-brain barrier garage door, finding ways to allow for at least temporary passage of helpful cancer drugs. One major consideration is that, when the blood-brain barrier is open, not only can good things come into the brain, but it might also let other things out of the brain that can cause problems. This can make it challenging to specify exactly where and for how long is it safe enough to do so.

Here are five ways in which they can do so.

Mannitol

This compound found naturally in fruits and vegetables can change the pressure of the blood-brain barrier to open it up temporarily. It can help in conjunction with chemotherapy to improve drug penetration as well as delivery of stem cells or other substances to the brain. However, McCarty points out that “it’s almost like a bomb” breaking through. This is considered a very intense approach because it is not very selective and can open up too many doors in the blood-brain barrier, causing side effects, such as inflammation and other neurological effects.

Direct delivery

Some drugs can be directly injected into the brain. Endovascular surgeon Christopher Young, M.D., Ph.D., is spearheading one of the most unique ways of tackling the blood-brain barrier. Young, who calls himself a plumber, inserts a tube up a patient’s arm through the blood vessels that can reach the brain and can deliver the drug directly next to its target. Researchers led by neurosurgeon Frederick Lang, M.D., along with neuro-oncologists Juan Fueyo, M.D., and Candelaria Gomez-Manzano, M.D., are also studying direct delivery of oncolytic viruses, which are genetically engineered viruses that specifically target and destroy cancer cells.

Focused ultrasound

This is a non-invasive technique using high-intensity targeted sound waves to temporarily open the blood-brain barrier in certain locations by creating tiny nano bubbles in the blood. The sound waves stimulate the bubbles, which expand and burst, causing temporary openings that allow nanoparticles to go through and release therapeutic agents. Neurosurgeon Jeffrey Weinberg, M.D., is studying focused ultrasound as a safe and effective way to disrupt the blood-brain barrier and deliver treatment.

Tumor-treating fields

These clinically approved non-invasive electric currents for glioblastoma use a patch placed on the skull that emits electric fields to damage the tumor cells and potentially slow tumor growth. Recent work done by neuro-oncologist Chirag Patel, M.D., Ph.D., shows that these electric fields also disrupt the blood-brain barrier and could potentially be used to improve delivery of chemotherapy drugs.

Extracellular vesicles

A team led by Betty Kim, M.D., Ph.D., and Wen Jiang, M.D., Ph.D., developed a new way to load messenger RNA (mRNA) into extracellular vesicles, which are small structures created by cells to transport biomolecules within the body. They can specifically program the vesicles to express certain proteins on the surface that serve as a docking mechanism for other proteins commonly found in glioblastomas. When they find and bind to the tumor cells, they can then release the mRNA inside of those cells.

UT MD Anderson’s Cancer Neuroscience Program encourages experts from many fields to look at the interactions between the nervous system and cancer. The goal is to further our understanding of the blood-brain barrier and its unique properties so that doctors can better personalize treatments and improve patient outcomes. 

“We continue to make advances in understanding the blood brain barrier in order to identify more effective ways to overcome it and deliver life-saving treatments for patients,” says McCarty.

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