“I just got the biopsy results back, and my little girl has an adrenal sarcoma,” wrote the owner of an 11-year-old Shih Tzu in an online support group for people whose pets have been diagnosed with cancer. “I’m so scared—for her and for myself. She’s my baby, my best friend, my companion. I know the time comes for everyone, but I don’t want her to hurt.”
Each year, about six million dog owners in the United States are dealt some devastating news. Their canine companion may have developed a soft tissue lump that hasn’t gone away, a wound that doesn’t seem to heal properly, or a constellation of different symptoms caused by any of the various types of cancers that affect dogs. The most common culprits are lymphomas, mast cell tumors, osteosarcomas, and melanomas—diseases that, together, are diagnosed in nearly half of all canines older than 10.
If those cancers sound familiar, it may be because they also affect patients of the two-legged variety. Humans and dogs share much of the same biology, a fact that not only helps to explain the susceptibility of each to cancer, but also opens the door for the discovery of new treatments for both species.
The survival rate for patients with gliomas, or cancers involving brain cells of the central nervous system, is extraordinarily low. Ted Kennedy, Beau Biden, and John McCain all succumbed to the most aggressive form of the disease, glioblastoma, within only two years after they were diagnosed. A similar fate awaits canine patients, especially among the more susceptible breeds: Boston terriers, Pugs, French Bulldogs, Shih Tzus, and Pekingese.
Gliomas are difficult to treat. Surgery is often not possible, because the brain has a very limited capacity to repair itself and tissue damage can cause irreparable harm. Chemotherapy drugs are typically unable to pass the blood-brain barrier, an interconnected network of capillaries that block foreign substances from reaching the brain. The most promising treatments for gliomas are cutting-edge immunotherapies, which represent a new frontier in cancer research and medicine.
Scientists at The Jackson Laboratory are studying dogs to make inroads in immunotherapy research that could save the lives of patients in both hospital oncology wards and veterinary clinics. The different approaches to fighting cancer by manipulating the body’s biological defense mechanisms can only be investigated by working with an animal model that has a fully developed immune system. Given that dogs live with people, and therefore are exposed to many of the same germs, cancer treatments developed in canines are likely to work for humans, too.
“Ultimately,” Principal Investigator Roel Verhaak, Ph.D., explained in a Jackson Laboratory blog post, “our project will benefit dogs and humans alike, and I’m extremely excited about this.” Before they find new treatments, though, Dr. Verhaak and his team must learn more about how gliomas respond to various agents of the immune system.
In blood, bodily fluids, stool, and tissue, researchers and physicians look for tumor markers, or substances that, in high concentrations, can indicate the presence of cancer. Decisions that concern treatment options are reached by measuring tumor markers like proteins, patterns of gene expression, or changes to DNA. Researchers at The Jackson Laboratory have identified molecular similarities between glioma markers in humans and dogs, which will allow them to better understand and interpret the results of canine immunotherapy trials while also improving the effectiveness of immunotherapies for human patients.
They also hope to discover why dogs develop brain tumors in the first place, which could potentially pave the way for preventative therapies. And in the process, new information will be gleaned about how gliomas develop in companion animals, adults, and also children because pediatric cancers have distinct pathogeneses (the ways in which the diseases progress).
For all of this research, The Jackson Laboratory is working with veterinary clinics to procure canine brain tumors, which are removed from dogs that have lost their battles with the disease. After the samples are donated, Dr. Verhaak’s lab performs whole-genome and RNA sequencing. Mapping the tumors’ complete DNA and RNA profiles will yield information about how the cancers evolve, how they respond to various drugs/therapies, and the processes in play, via evolutionary biology, that can explain why organisms develop them in the first place. Additionally, the discovery of similarities to or differences from the cancers’ human counterparts will inform treatment approaches for both species.
A similar research process is underway at The Jackson Laboratory for a different project: the Tallwood Canine Cancer Research Initiative, a biobank of dog tumors that will be shared with researchers from around the world. Veterinarians and pet owners who wish to contribute, can donate tumors that are removed as part of the normal course of the dogs’ cancer treatments. The researchers use them to create and sequence patient-derived xenograft models, which are then implanted in immunodeficient mice. By sequencing the cancer genome, they can find the DNA/RNA bases of the tumors, as well as their mutation statuses and structural changes. And by studying the canine tumors’ pathogeneses in mice, they can see how the diseases change over time and which treatments are most effective.
Jackson Laboratory researchers expect the biobank will unlock new clues about how differences in the canine genome predispose certain dog breeds to certain types of cancer. Studying the corresponding regions in human genomes may, accordingly, help to explain cancer susceptibility in people.
“The information gained from this program,” says Principal Investigator and Scientific Director Charles Lee, Ph.D., FACMG, “may uncover new insights into regions of the human genome that modulate specific types of human cancers; especially cancers that are less common in humans but much more frequently found in certain dog species.”