A Path Forward for Overcoming the Blood–Brain and Blood–Tumor Barriers

<p>Figure: Physical and chemical properties of the blood–brain barrier (BBB) structure.</p>

Figure: Physical and chemical properties of the blood–brain barrier (BBB) structure.

Getting cancer drugs to their target can be difficult under the best of circumstances, but in the case of brain cancer the challenge is compounded by the blood-brain barrier- a semipermeable barrier that has evolved to keep the brain “safe” from toxins in the blood. The effectiveness of that barrier also prevents many cancer-fighting drugs and therapies from reaching their intended targets.

Costas Arvanitis, an assistant professor in the George W. Woodruff School of Mechanical Engineering and the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory and his collaborators, Gino Ferraro and Rakesh Jain from Massachusetts General Hospital and Harvard Medical School, were invited by Nature Reviews Cancer (NRC) to write a review article on the topic, synthesizing and consolidating the existing body of research and offering recommendations for future areas of study that could act as a guide for other researchers and scholars both inside and outside the field. That review was published on October 10, 2019.

“We felt it was extremely important to be able to summarize what has been done in this field, identify components that are important, and, based on that knowledge, try to determine the next big questions that must be answered to move the field forward,” said Arvanitis. “There are many people studying cancer, but they may not have had an opportunity to study in depth the intricacies of the blood-brain barrier.

Arvanitis also espoused the benefits of looking at the blood-brain barrier from an engineering standpoint.

“In nanomedicine you can spend a lot of time identifying new molecules targeting different pathways to treat cancer, but the problem is that systemically administered drugs may essentially never reach the cancer cell because of the blood brain barrier. This is fundamentally an engineering problem. We must understand the biological properties of the system so we can design rational therapies and strategies to overcome it.”

Arvanitis has been working with colleagues on a solution that involves using targeted ultrasound to massage the barrier in a way that increases its permeability. A 2018 study by his group and his collaborators, which was published in Proceedings of the National Academy of Sciences (PNAS), demonstrated the promise of the technique and also highlighted the need for further understanding on the challenges posed by the blood-brain barrier.

The research review highlighted a range of areas for future study. First, the need for deeper understanding of the structure and function of brain vessels within the tumor microenvironment. Second, its rate-limiting role in emerging immunotherapeutic approaches and how targeted drug delivery strategies like focused ultrasound can overcome this bottleneck. The review also goes on to recommend incorporating systems biology and mathematical modeling to identify new therapeutic techniques and the rational design of therapeutic interventions.

“We think that this paper has the potential to shape research moving forward. This is the first review specifically about brain cancer and the blood-brain barrier,” added Arvanitis. “We hope that it can serve as a guide for others in this research field and result in improved outcomes for patients.”

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Walter Rich