A dogged pursuit of aggressive brain cancer

Dogs are helping researchers better understand the biology of brain tumors in hopes of developing better treatments for high-grade gliomas

BY Meagan Raeke

Kristin Patrick and her husband, Robert Watson, have two sons, but say Sadie was their “first baby.”
photos by Wyatt McSpadden

You probably wouldn’t guess that Sadie Watson has much in common with anyone at MD Anderson. After all, Sadie is a 9-year-old French bulldog and beloved family pet.

But she’s also facing the same diagnosis as many patients in the Brain and Spine Center: a brain tumor called a glioma.

It turns out that the same brain tumors that affect humans are found in dogs.

Now, physician-scientists from MD Anderson and Texas A&M University are teaming up to help man and man’s best friend.

A common bond

Current therapies simply aren’t very effective at treating very aggressive gliomas, such as grade IV glioblastoma, which spread very quickly throughout the brain.

And the survival rate is poor in both humans and dogs.

“We have the same struggles in that these gliomas in dogs are really hard to treat,” says Jonathan Levine, D.V.M., professor and department head of Small Animal Clinical Sciences at Texas A&M College of Veterinary Medicine & Biomedical Sciences, where Sadie is a patient.

But scientists know tumors from both species look almost identical on MRI scans and under the microscope. And based on this, the National Cancer Institute (NCI) created a comparative brain tumor consortium in 2015 to evaluate canine brain cancer as a model for human disease.

“The big question is: ‘Are human and canine high-grade gliomas genetically the same?’” says Amy Heimberger, M.D., professor of Neurosurgery at MD Anderson and co-leader of the Glioblastoma Moon Shot™.

To find the answer, she’s leading a multi-institutional NCI-funded study to characterize genetic alterations in canine glioma and identify immune responses in these tumors. Heimberger is also a dog lover, with a collie named Duke, a West Highland terrier named Winston and a long-haired dachshund named Millie.

Levine and brain tumor genomics expert Roeland Verhaak, Ph.D., professor and associate director of Computational Biology at The Jackson Laboratory in Connecticut, are co-investigators in the firstof-its-kind study. Levine has two dogs: Ramsey, a bloodhound; and Lucy, a border terrier. Verhaak has a Chihuahua named Lola.

Verhaak is currently analyzing data taken from whole-genome and RNA sequencing of 90 tissue samples from dogs with brain tumors. The long-term goal is to develop a safe and effective immunotherapy for both dogs and people with high-grade gliomas.

“These dogs, not only do they stand to benefit, but they represent an amazing opportunity to understand the biology of brain tumors, to understand how tumors evade drugs and to understand the immune response,” Levine says.

Sadie

A better model

All new cancer drugs are tested for safety and effectiveness in the lab – often in engineered mouse models – before they are approved for clinical trials in humans or dogs.

“Pre-clinical studies can look fantastic in mice, but fall apart in humans,” Heimberger explains.

For a cancer like glioblastoma, which has a five-year survival rate of less than 10%, this is exceedingly frustrating.

“I want to reduce the cost and futility of clinical trials. When you have a patient facing something this dire, you want to offer them something with a good chance of success.”

The current model system is imperfect: Mice do not grow brain tumors on their own. Their tumors are small, sometimes microscopic. They live in a sterile environment. And their immune response is biased, making it difficult to accurately assess immunotherapies.

Dogs, on the other hand, spontaneously develop large brain tumors. They have a natural immune response to cancer. And they live in the homes of their human families.

A shared hope

As Sadie’s owner Kristin Patrick says, “When you love a pet so much, they become part of your family.” Patrick and her husband, Robert Watson, have two young sons, but Sadie was their “first baby.”

When Sadie was diagnosed in July 2016, Patrick and Watson decided she would undergo brain surgery to remove the tumor, donate the tissue for analysis and enroll in a clinical trial. Their perspective as parents and researchers (both are assistant professors in the Microbial Pathogenesis and Immunology department at Texas A&M Health Science Center College of Medicine) shaped the treatment decision.

“Participating in science is essential to move these therapies forward for families,” Patrick says. “If our actual baby had a brain tumor – I can’t even fathom that.”

As the researchers analyze tumor tissue samples from Sadie and other dogs, they will look for genetic mutations and immune responses known to occur in human brain tumors.

If the results show that canine brain tumors are indeed a good model for human brain tumors, then clinical trials in man’s best friend could reveal which new immunotherapies have the best chance of success for humans.

“Cancer is horrible for anyone affected by it, whether that’s a dog or a person,” Levine says. “There’s a huge opportunity here to develop something that helps dogs and also helps people.”

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