Grant puts research team on track to treat brain cancer

Pictures of dogs and their smiling owners line a wall of John Robertson’s office in Kelly Hall.

Each canine, from Spanky, the Boston terrier, to Lena, the miniature schnauzer, battled brain cancer and lived longer than expected, thanks to a clinical trial at the Virginia-Maryland College of Veterinary Medicine at Virginia Tech.

In the next few years, Robertson, a research professor of biomedical engineering and mechanics at Virginia Tech, hopes to post pictures of people on his wall.

A recently awarded $9.2 million grant from the National Institutes of Health’s National Cancer Institute will help a team that includes Robertson and other engineers, cancer researchers, surgeons, and veterinarians from Virginia Tech and Wake Forest University to test the same treatment methods on humans.

The five-year grant will fund four different approaches to treating brain cancer, specifically glioblastoma, the most common and deadliest form of brain cancer in adults.

“The goal of our work has always been to get critical therapies to people,” Robertson said. “This grant will provide us with the resources to take this over the line.”

Most of the researchers work within the Virginia Tech-Wake Forest University School of Biomedical Engineering and Sciences. The school is a joint graduate program that includes faculty from Virginia Tech’s College of Engineering, the Wake Forest School of Medicine, and the College of Veterinary Medicine. It is supported, in part, by the Institute for Critical Technology and Applied Science at Virginia Tech.

Some researchers at the Virginia Tech Carilion Research Institute also are developing new approaches to treating glioblastoma.

Fifteen years ago, Virginia Tech and Wake Forest researchers set out to find a treatment for glioblastoma, which has a median human survival rate of about 14 months in its most aggressive form, according to the American Brain Tumor Association. Monthly trips to Wake Forest in Winston-Salem, North Carolina, from Blacksburg are typical for the Virginia Tech team.

Waldemar Debinski, a professor of cancer biology, radiation oncology, and microbiology and immunology at Wake Forest Baptist Medical Center, is the principal investigator for the grant, which is the largest the group has received. Debinski also directs the Brain Tumor Center of Excellence at Wake Forest Baptist.

Though the team’s research represents different methods, all are synergistic.

“This project really does epitomize the strengths of the team,” said Rafael Davalos, a professor of biomedical engineering and mechanics at Virginia Tech who co-wrote the grant.

Davalos leads one of the four projects, with a technology that he created called electric field ablation. It sends nonthermal voltage into a cell’s protective membrane, identifying malignant cancer cells and killing them. Scott Verbridge, a tumor micro environment specialist and assistant professor of biomedical engineering and science at Virginia Tech, works with Davalos researching ways to identify and destroy only malignant cells, without harming healthy cells.

For another project, Debinski and his team are developing candidate drugs that will target and eliminate tumor compartments that are primarily responsible for tumor progression and are resistant to treatment.

Chris Rylander, a former associate professor at Virginia Tech and leader of another project, is developing a fiberoptic microneedle device that can be used to insert a chemotherapy drug into cancerous tumors. Rylander now is an associate professor in the Department of Mechanical Engineering at the University of Texas at Austin.

Akiva Mintz, formerly of Wake Forest, who now is a professor of radiology at Columbia University Medical Center, leads a fourth project. His group is developing methods that would allow drugs to get into the brain from the blood and using noninvasive molecular imaging that traces the way a drug is distributed throughout the body.

All of the projects include cancer therapies that have been tested in dogs in a series of clinical trials led by John Rossmeisl, a neurosurgeon and a professor of neurology at the Virginia-Maryland College of Veterinary Medicine. With the treatment, some of the dogs’ tumors shrank, and some canines lived a year longer than expected, he said.

“The canine model is as close as you can get to doing it with a person,” said Rossmeisl, explaining that the FDA has said that it is willing to use the dog data from the trials as a safety indicator for developing human trials.

"The projects of the grant are novel in that they use newer, improved versions of the technologies or drugs based on results obtained in the lab as well as in clinical trials," he said. "We are evaluating various combinations of these unique approaches as they may have synergistic and additive anti-cancer effects."

Graduate students, including those working toward master’s degrees, Ph.D.s, and postdocs, are a part of these research teams.

The NCI grant will make it possible to begin clinical trials in adults within the next three years, said Davalos.

This work hits home with many of the researchers who have lost family members and friends to cancer of all kinds, including Davalos’ father and Robertson’s mother, who died as a result of a brain tumor.

Davalos said he hopes the results of this work will increase the median survival rate of glioblastoma patients and ultimately, improve their quality of life.

“You want to try to make an impact,” he said.

Written by Jenny Kincaid Boone