Tackling brain cancer is complicated, but groundbreaking new research could help add another tool to the cancer-fighting arsenal.
A team from Georgia Tech and Virginia Tech published a paper in APL Bioengineering in May that explores a new option that could one day be used to attack glioblastoma, a deadly, fast-growing brain tumor.
This work, funded by grants from the National Institutes of Health, builds on previous research into high-frequency irreversible electroporation, better known as H-FIRE. H-FIRE is a minimally invasive process that uses nonthermal electrical pulses to destroy cancer cells.
Treating any type of cancer isn’t easy, but when it comes to brain cancers, the blood-brain barrier poses an additional challenge. The barrier defends the brain against toxic material, but that’s not always a good thing.
“Mother Nature designed it to prevent us from poisoning ourselves, but unfortunately, the way it works also prevents about 99 percent of all small molecule drugs from getting into the brain and reaching adequate concentrations to elucidate their therapeutic effect. This is particularly true for chemotherapeutics, biologics or immunotherapies,” said John Rossmeisl, professor of neurology and neurosurgery at the Virginia-Maryland College of Veterinary Medicine. Rossmeisl is one of the paper’s co-authors.
The square wave typically used with H-FIRE serves a dual function: it disrupts the blood-brain barrier surrounding the tumor and kills cancer cells. However, this was the first study to use a sine wave to disrupt the barrier. This new modality is called burst sine wave electroporation (B-SWE).
The researchers used a rodent model to study the effects of the sine wave versus the more conventional square wave. They found that the sine wave caused less damage to cells and tissues, but greater disruption of the blood-brain barrier.
In some clinical cases, both ablation and disruption of the blood-brain barrier would be ideal, but in others, disruption of the blood-brain barrier may be more important than cell destruction. For example, if a neurosurgeon were to remove the visible tumor mass, the sine waveform could potentially be used to disrupt the blood-brain barrier surrounding the site, allowing drugs to enter the brain and kill the last cancer cells. B-SWE could cause minimal damage to healthy brain tissue.
Research indicates that conventional square waves show good disruption of the blood-brain barrier, but this study finds that the disruption of the blood-brain barrier is even better with B-SWE. This could allow more cancer drugs to access the brain.
“We thought we had solved that problem, but this shows that with a little forward thinking, there are always potentially better solutions,” said Rossmeisl, who also serves as associate chair of the Department of Small Animal Clinical Sciences.
During the study, the researchers encountered a stumbling block: in addition to increased disruption of the blood-brain barrier, they found that the sine wave also caused more neuromuscular contractions. These muscle contractions risk damaging the organ. However, by adjusting the dose of B-SWE, they were able to reduce the contractions and provide a level of disruption to the blood-brain barrier similar to that of a higher dose.
The next step in this research is to study the effects of B-SWE using an animal model of brain cancer to see how the sinusoidal waveform compares to the conventional H-FIRE technique.
The project was led by first author Sabrina Campelo while she was completing her PhD in the School of Biomedical Engineering and Sciences at Virginia Tech-Wake Forest University. Campelo is now a postdoctoral researcher in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University.