Virginia Tech veterinary neurologist helps establish shared ‘life history’ of brain cancer in dogs, people

By Mindy Quigley

Humans and dogs share many aspects of their lives: food, homes, and a deep bond of mutual affection. Although these common bonds bring joy and comfort, one connection between the two species is decidedly not positive. Both dogs and humans are uniquely susceptible to a devastating, aggressive brain tumor referred to as a glioma.

Companion dogs develop glioma brain tumors spontaneously at about the same rate as people. The cancer is rare in both humans and animals, but upon its appearance, it tends to be swift-moving and notoriously resistant to treatment.

Even with the most advanced medical therapies, glioma tumors killed U.S. senators John McCain and Ted Kennedy, along with then-Vice President Joe Biden’s son, Beau. Despite the attention on adult sufferers of the disease, gliomas can also affect children, and the prognosis is often just as dire.

A group of researchers, including John Rossmeisl Jr., the Dr. and Mrs. Dorsey Taylor Mahin Professor of Neurology and Neurosurgery at the Virginia-Maryland College of Veterinary Medicine at Virginia Tech, recently set out to determine the depth of the commonalities between canine and human gliomas — a connection that has major implications for treating these intractable tumors.

The team, led by computational biologist Roel Verhaak of the Jackson Laboratory, a nonprofit biomedical research institution, analyzed tumor samples from dozens of gliomas in adults, children, and dogs to compare their molecular profiles.

The researchers found a remarkable degree of similarity, particularly between pediatric and canine tumors. The locations of genetic mutations were often the same, as were disease processes, such as the way gliomas alter DNA’s ability to repair itself and the timing of when the mutations themselves arise.

These findings, published as “Comparative Molecular Life History of Spontaneous Canine and Human Gliomas” in the journal Cancer Cell, are both significant and original.

“The paper demonstrates that changes that are critical for brain tumor formation, including genetic mutations and acquired modifications in gene activity, are similar between human and canine brain cancers,” Rossmeisl said. “Understanding these complex changes is a fundamental first step.”

Using the knowledge they gained in their comparative approach, researchers are already beginning to develop and evaluate novel treatment approaches for brain cancer. In addition, the team’s findings support the use of dogs as a model for human gliomas, an especially important consideration given the difficulties of modeling cancer in the laboratory.

Cells in a petri dish often fail to mirror the way cancer behaves in a patient’s body, and serious ethical issues are invoked when inducing cancers in healthy laboratory animals.

Because gliomas arise spontaneously in dogs and because the current, standard treatments often do not meaningfully improve the prognosis, experimental therapies aimed at dogs can help identify treatments that could evolve into promising human clinical trials.

Dogs’ shorter lifespans mean that canine cancer tends to develop in a more compressed timescale than in humans, which enables therapies to be tested and outcomes to be assessed more rapidly.

Two such trials are currently ongoing at the veterinary college. The first uses a technology called H-FIRE (high-frequency irreversible electroporation) to destabilize and kill cancer cells with short, targeted bursts of electrical energy, causing an immune reaction that can “mop up” remaining cancer cells.

Another large-scale collaboration, which recently received a share of a $9.2 million grant from the National Institutes of Health’s National Cancer Institute, is testing a molecularly targeted chemotherapy. The drug in the study targets proteins on the surface of glioma cells that had previously been shown to be nearly identical between human and canine gliomas.

According to Rossmeisl, “Our results effectively position preclinical models of spontaneous canine glioma to better understand glioma drivers, those alterations that give cells a fundamental ability to transform into cancer.”

For Rossmeisl, a veterinary neurologist, each of the data points in the new study has a special significance: He treated the dogs whose tumor samples were analyzed. Moreover, each sample — whether taken from a child, an adult, or a dog — had a unique “life history.” These patients’ contributions may help to write different endings for the life stories of the next generation of brain tumor patients.

Mindy Quigley is the clinical trials coordinator in the Department of Small Animal Clinical Sciences at Virginia Tech.