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Why is brain cancer so difficult to treat?

Despite medical advancements, treating brain cancer is still particularly challenging. We asked University of Minnesota Health experts to explain the difficulties—and why they have hope for patients.
University of Minnesota Health Neurosurgeon Matthew Hunt, MD, FRCS, FAANS, and Neuro-Oncologist Elizabeth Neil, MD, treat brain cancer and brain tumor patients. Despite recent medical advancements, brain cancer is still challenging to treat. We asked Neil and cancer researcher David Largaespada, PhD, to explain why.

Why is brain cancer so difficult to treat? It’s a simple question that comes with many not-so-simple answers.

For decades, medical advancements have improved outcomes for patients diagnosed with a variety of cancers. Despite this substantial research and innovation, treating brain tumors are still a challenging target.

The five-year survival rate for all brain tumors—including benign tumors—is roughly 33 percent, according to the National Cancer Institute.

That number drops significantly for diseases like glioblastoma multiforme, the most malignant brain tumor type. Glioblastoma multiforme has a five-year survival rate of roughly 5 percent, according to University of Minnesota Health Neuro-Oncologist Elizabeth Neil, MD.

A number of factors make brain cancer a challenging disease to treat, including the brain’s natural defenses, accessibility of the tumors and their ability to spread rapidly and the complexity of brain cancer. We asked Neil and David Largaespada, PhD, a cancer researcher at Masonic Cancer Center, to tell us more.

Breaking through the blood-brain barrier

The brain is protected by a blood-brain barrier, a network of tiny blood vessels that serves as a gatekeeper for the brain. The barrier allows the brain to absorb necessary nutrients, but prevents potentially harmful substances from entering the brain tissue. Unfortunately, also works against many types of cancer drugs, effectively blocking them from reaching their target: the brain tumor.

“The tumor cells that we need to kill are behind this blood brain barrier, so many potentially useful drugs never actually get to them,” Largaespada said.

To penetrate the blood-brain barrier, researchers must either redesign cancer drugs or co-treat the tumors with other drugs that reduce the effectiveness of that barrier so that the cancer-killing drugs can get through.

The challenges of surgical removal

Surgeons must be very careful when operating on brain tumors. When treating other cancers, surgeons can remove a “margin” of normal tissue around the tumor to ensure that all cancerous cells are taken out. The sensitivity of the brain means that taking a margin around the tumor is often impossible.

“Someone can have a mastectomy and have the entire tumor removed — or you can survive with a large portion of your liver being removed,” Neil said. “But the brain is a delicate organ. You have to be very careful of how much you're taking out and what pieces are being removed.”

To make matters more challenging, brain cancer cells don’t like to stay put. Tumors often grow tentacle-like projections that extend outward from the central tumor into normal brain tissue. These thin extensions are especially difficult to remove. In other cases, the brain cancer has spread to other separate locations in the brain.

Largaespada received a grant from the National Cancer Institute to study how brain cancer cells migrate and spread within the brain.

“Cells move away from the tumor in part so that they can get more nutrients and more space to grow,” he said. “If we can actually target migration, we might have a therapeutic effect in these brain tumors.”

Brain cancer complexity

Highly malignant brain tumors are the chameleons of the cancer world.

“It’s not that you’re fighting just one cancer when you’re talking about highly malignant brain tumors. You’re talking about multiple different mutations driving different cancer cells within the brain tumor,” Neil said. “If you target one mutation and kill off one group of cancerous cells, that still leaves other groups that are unaffected and continue to thrive.”

As researchers continue to understand the complexity of brain tumors, they’ll be able to zero in on the unique vulnerabilities of each cancer cell type and then destroy them with a “unique cocktail” of drugs. This is the crux of some of Largaespada’s research.

“Just like Superman is sensitive to Kryptonite and normal people aren’t, cancer cells have their own unique weaknesses that depend on their mutations,” Largaespada said. “We’re trying to find and exploit those.”

Hope for the future

Although brain cancer treatment presents a number of challenges, Largaespada and Neil are hopeful. The University of Minnesota brings together multidisciplinary research teams that collaborate across a variety of fields and specialties. The teams working to treat brain tumors include doctors and clinicians, technicians, care coordinators, basic research scientists and more. Our care providers also offer access to innovative clinical trials that expand care options for brain cancer patients.

“I’m hopeful about the future. We’re testing more ideas than ever before in order to improve treatments for brain cancer—and some of these ideas are starting to show real promise,” Largaespada said. “I think in the near future we’ll be seeing more and more success stories.”