The lack of a diagnostic ability to decide how to best treat aggressive brain tumors, particularly glioblastomas, a very deadly cancer, has vexed researchers for decades.
Getting drugs across the blood/brain barrier is a challenge, and many brain tumors are difficult to treat because they spread through the brain, often with tendrils that reach deep into its recesses.
But UNC Lineberger’s Shawn Hingtgen, PhD, and his lab team have developed a method they call a “slice platform” that may help resolve many of the obstacles that clinicians face when choosing the best treatment for their brain tumor patients.
A key member of Hingtgen’s research team is Andrew Satterlee, PhD, the brain slice program manager, and a brain cancer survivor who was diagnosed when he was 20, nearly 15 years ago.
Part of his initial treatment involved surgical removal of a rare, heterogenous germ cell brain tumor the size of a golf ball. His surgeon was University of California San Francisco’s Mitchel Berger, MD, FACS, FAANS, whom Satterlee later deemed the ‘godfather of brain surgeons.’
“In a cool, full-circle moment, I met him as a peer at the Society for Neuro-Oncology’s annual meeting in 2017,” Satterlee said.
Patient and researcher
Satterlee’s tumor was rare, so choosing a chemotherapy to prevent recurrence was fraught as there was wide disagreement among experts on what course of action was best.
Satterlee ultimately followed the advice of a renowned pediatric neuro-oncologist who, by coincidence, was also a germ cell brain tumor survivor.
The oncologist urged the family to consider moving from what the standard of care had been to what the standard of care was becoming. Satterlee’s brush with mortality eventually led him down his current career path, convinced that clinicians need a better way to choose the best treatment for each patient because, as in his case, it shouldn’t have been up to him to make that choice.
Putting experience into practice
Hingtgen and Satterlee have developed a tool that should help physicians design better treatment plans and make better drug choices. They also think the tool can help drug development companies advance their therapeutic processes.
Hingtgen’s team developed a diagnostic procedure that involves placing cells from a patient’s resected tumor onto a slice of rodent brain that is kept alive by the culture medium beneath it, allowing the cells to engraft in the rodent tissue and grow.
Using a variety of different assays and techniques, the researchers can test different drugs on the engrafted tissue and determine which drug works best.
The research team recently filed a patent on their process and they are starting to partner with industry to advance their techniques. They are also almost finished developing a protocol for a feasibility clinical trial — a first step toward validating the tool in a clinical setting to guide the treatment.
Working toward similar goals, one of UNC Lineberger’s newest recruits, Dominique Higgins, MD, PhD, a neurosurgical oncologist specializing in the treatment of brain tumors, is pursuing complementary research with his surgical patients and is invested in the potential outcomes Hingtgen’s team is working on.
“My own lab works closely with Drs. Hingtgen and Satterlee’s, and I’m excited about harnessing this technology and applying it to brain metastases from primary sites, such as breast and lung cancer, in addition to studying the metabolism of primary brain tumors,” Higgins said.
Philanthropy moves science forward
Hingtgen noted that their unique translational research activities between the lab bench and a patient’s bedside sit in an odd space that is difficult to get funded. While the National Institutes of Health extensively supports basic research, philanthropic support for the nuts and bolts of their translational efforts could be key in moving from the lab to people, he said. And they’re talking about relatively small funding compared to the millions of dollars it can take to support a large clinical trial.
“If everything worked perfectly, we would enroll every person diagnosed with a brain tumor in our studies. But we need to show we can do this experiment in the controlled environment of a feasibility study. If that study goes well, the next step would be a trial to see if guided treatment was beneficial and that would also help set the stage for regulatory approvals,” Hingtgen said.
The researchers believe that their research would not have been possible at other institutions. “The collaborations between UNC Lineberger, the Eshelman School of Pharmacy and institutions across campus, including translational labs and clinics, have been amazing — the interdisciplinary team that we have is unbelievable,” Hingtgen said. “And the best part of this collaboration is that it should ultimately benefit our patients.”