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Trish Rockett

Dogs and their owners are said to look alike, but that resemblance is more than skin deep.

They also have genetic similarities that extend to <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9852553/" target=_blank>cancerous tumors</a> and make dogs prime candidates for clinical trials that are pushing forward development of cancer drugs for both canines and humans, especially in the past decade, scientists say.

Compelling genetic data, increased funding and growing collaborations between veterinarians and oncologists were things “we dreamed about 10 years ago,” said <a href="https://ccr.cancer.gov/staff-directory/amy-k-leblanc" target=_blank>Amy LeBlanc</a>, director of the Comparative Oncology Program at the National Cancer Institute (NCI). “Now it’s becoming reality.”

<a href="https://www.nature.com/articles/s12276-023-00977-3" target=_blank>Comparative oncology</a> — the study of <a href="https://academic.oup.com/mbe/article-abstract/37/1/11/5613170?redirectedFrom=fulltext" target=_blank>cancers in companion animals</a> that researchers hope will translate to human treatments — has picked up steam because a vast majority of <a href="https://academic.oup.com/biostatistics/article/20/2/273/4817524" target=_blank>cancer clinical trials fail</a>.

<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3902221/" target=_blank>Mouse models</a>, which are commonly used, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9714416/" target=_blank>don’t really translate</a> all that well to success in humans, said <a href="https://vetmedbiosci.colostate.edu/directory/member/?id=steven-dow-1009" target=_blank>Steven Dow</a>, professor of immunology and director of the Center for Immune and Regenerative Medicine at Colorado State University. One of the reasons is that mice don’t develop cancer on their own, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3533445/" target=_blank>they require genetic manipulation</a>. The dog cancer model is a way “to lessen the risk of failure in the eventual human trial,” he said.

Years ago, researchers figured it may be a good idea to study dogs, thinking, “dog gets a lump, people get a lump, surely it must be similar,” said <a href="https://www.vet.upenn.edu/people/faculty-clinician-search/NICOLAMASON" target=_blank>Nicola Mason</a>, professor of medicine and pathobiology at the University of Pennsylvania School of Veterinary Medicine.

Now, though, there’s evidence that dog and human tumors not only look the same under a microscope — <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9852553/" target=_blank>mutations</a> in the same genes often drive their emergence and spread. “In some cases, it really is the exact same mutation,” Mason said. “Remarkable, right? Crazy.”

Studying dogs has some other advantages such as:

There are fewer confidentiality concerns.

Trials in dogs can provide cleaner data about a drug’s efficacy.

Dogs make for better clinical trial subjects because they are exposed to much of our environment — the same air, microbes and water — and a number of environmental factors have been linked to <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3521879/" target=_blank>cancer in humans</a> and in <a href="https://onlinelibrary.wiley.com/doi/10.1111/vco.12771" target=_blank>dogs</a>. Compare that with “a mouse in a cage down in a basement somewhere,” Mason said.

Genetic and other medical confidentiality concerns with human data also aren’t an issue with dogs, making data sharing easier.

Another important advantage is that trials in dogs offer cleaner data. To be eligible for a clinical trial of a new drug, a person with cancer <a href="https://www.ncbi.nlm.nih.gov/books/NBK50895/" target=_blank>typically needs to fail</a> the standard of care — often chemotherapy — or to combine the standard of care with the trial drug, “because it’s considered unethical to give a person something experimental without having provided them the best treatment that we know works,” said <a href="https://wag.app.vanderbilt.edu/PublicPage/Faculty/Details/47143" target=_blank>Alexander Bick</a>, assistant professor of medicine at Vanderbilt University School of Medicine.

Dog owners, though, don’t have to accept a prescribed standard of care, said Cheryl<a href="https://vet.tufts.edu/people/faculty/cheryl-london-dvm-phd-dacvim" target=_blank> London</a>, professor of comparative oncology and associate dean for research at the Cummings School of Veterinary Medicine at Tufts University. Dogs can go right into a clinical trial without having their immune system already worn down by earlier treatments, thereby providing clearer data on the effects of a new therapy.

A thriving field of canine and human cancer research

Last year, Dow and <a href="https://vetmedbiosci.colostate.edu/directory/member/?id=dan-regan-33234" target=_blank>Dan Regan</a>, assistant professor of microbiology, immunology and pathology at Colorado State University, both led <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8866227/" target=_blank>a successful clinical trial</a> in dogs with <a href="https://www.hopkinsmedicine.org/health/conditions-and-diseases/sarcoma/osteosarcoma" target=_blank>osteosarcoma</a>, a common form of <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4330401/" target=_blank>canine bone cancer</a>. The trial showed that the human blood pressure medication, losartan, combined with the canine cancer drug, toceranib, could stabilize and even shrink tumors in half of the dogs treated.

Based on those findings, losartan and a human drug similar to toceranib, <a href="https://onlinelibrary.wiley.com/doi/10.1111/vco.12799" target=_blank>sunitinib</a>, have entered phase I clinical trials in human <a href="https://clinicaltrials.gov/ct2/show/NCT03900793" target=_blank>patients with osteosarcoma</a>, which is rare but most likely to afflict children and young adults.

Canine clinical trials with <a href="https://jitc.bmj.com/content/10/Suppl_2/A877" target=_blank>losartan and toceranib</a>, meanwhile, are continuing and now include the anti-inflammatory drug, ladarixin. If ladarixin shows a significant benefit, that could influence the trajectory of the current human trial, Dow said.

Maisy, a golden doodle, was enrolled in the ladarixin trial after being diagnosed with osteosarcoma. Maisy had the tumor removed, was put on the three-drug regimen and over a year later, remains cancer free.

“I’m grateful that we have this time with Maisy,” said her owner, Trish Rockett. “And just knowing that this research being done with dogs is actually helping kids, too — it’s just amazing.”

For years, <a href="https://www.washingtonpost.com/national/health-science/new-tricks-in-canine-cancer-research-may-improve-treatments-for-humans-too/2016/11/26/837dcd52-a4fc-11e6-8042-f4d111c862d1_story.html" target=_blank>Mason has also been working on treatments for osteosarcoma</a> and recently wrapped up a successful phase III canine clinical trial with a listeria vaccine that tricks the <a href="https://ostherapies.com/" target=_blank>immune system</a> into fighting off the cancerous cells. She and her colleagues found that canines treated with the vaccine had a significantly higher survival rate and a decreased chance of disease progression. A<a href="https://clinicaltrials.gov/ct2/show/NCT04974008" target=_blank> human clinical trial</a> based on that work is now in phase II, meaning the vaccine has proved to be safe and is being tested for efficacy and potential side effects.

The pediatric oncology community was aware of this canine clinical trial, said LeBlanc, who ran it alongside Mason. “It really has value when you feel like the path you’re going down is of interest to the physician world,” LeBlanc said, “because you want your work to impact as many people — and species — as possible.”

Treatments for rare cancers such as osteosarcoma are difficult to find — a lack of funding and small number of patients can make conducting <a href="https://www.fda.gov/patients/rare-diseases-fda" target=_blank>clinical trials</a> tough. But <a href="https://www.frontiersin.org/articles/10.3389/fvets.2021.734965/full" target=_blank>dogs develop osteosarcoma</a> about 10 times more often than people, so clinical trials in dogs could help researchers home in on the treatment most likely to succeed in humans, while at the same time find a cure for our beloved companions.

“I think everybody likes the idea that they can help dogs, right?” Mason said.

There are dozens of ongoing <a href="https://ebusiness.avma.org/aahsd/study_search.aspx" target=_blank>canine clinical trials</a> for a variety of cancers, and increased funding from <a href="https://ebusiness.avma.org/aahsd/study_search.aspx" target=_blank>programs</a> such as the <a href="https://www.cancer.gov/research/key-initiatives/moonshot-cancer-initiative" target=_blank>Cancer Moonshot</a> are helping this growth. Ten years ago, LeBlanc said, nobody would have thought that NCI would have funded canine clinical trials at that level.

The creation of <a href="https://ebusiness.avma.org/aahsd/study_search.aspx" target=_blank>data repositories</a> such as the NCI’s <a href="https://caninecommons.cancer.gov/#/" target=_blank>Integrated Canine Data Commons</a>, which launched<a href="https://www.nature.com/articles/s41684-021-00741-y" target=_blank> in 2020</a>, is making collaboration between veterinarians and clinicians easier.

Bick is interested in mutations in blood stem cells that can progress to blood cancer in some people, but not all, for reasons unknown to scientists.

When Bick learned that blood cancers are relatively common in dogs, he contacted London and Elinor<a href="https://www.broadinstitute.org/bios/elinor-karlsson%22%20/t%20%22_blank" target=_blank> Karlsson</a>, director of Vertebrate Genomics at the Broad Institute of MIT and Harvard, and associate professor of bioinformatics and integrative biology at UMass Chan Medical School.

Bick and his colleagues had already developed an <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944936/" target=_blank>inexpensive test</a> to look for these pre-blood cancer mutations in humans, but with Karlsson and London, he was able to redesign it to look for an overlap between dogs and humans.

They found that dogs “have some of the same pre-blood cancer mutations that humans do,” Bick said. They’re continuing to monitor the dogs with pre-blood cancer mutations with the hope that one day they might be able to predict and prevent disease progression in both people and canines.

Advances in genetic sequencing and data sharing have also led to the formation of companies such as FidoCure — where London, Mason and Karlsson are paid members of the advisory board. The company analyzes dog tumors for mutations and, based on the data, recommends — and sends, if requested by the owner — a drug treatment to the dog’s veterinary clinic, which must be one of the clinics in FidoCure’s network. The dog’s owner also can take that recommendation to a clinic outside the network.

The results of those suggested treatments are reported back to FidoCure by the clinics and uploaded to FidoCure’s database, helping inform care for other dogs who have tumors with similar genetic profiles. FidoCure is hoping to soon collaborate with the Integrated Canine Data Commons, said company chief executive Christina Lopes, and has developed a tool called Fetch that will soon allow clinicians and biopharmaceutical collaborators to access FidoCure’s data.

Bick, who was surprised to find himself working with dogs, says this work has shown him the importance of canine companions in pushing cancer trials forward.

It also has him thinking about what we might learn from other animals that naturally develop diseases also affecting humans. At zoos, veterinarians will be able to tell you things such as, “Oh, yes, the black-footed ferret, they always get <a href="https://pubmed.ncbi.nlm.nih.gov/17469273/" target=_blank>amyloidosis</a>, which causes <a href="https://www.science.org/doi/10.1126/sciadv.add2671" target=_blank>Alzheimer’s disease</a> in humans,” Bick said. “Like, really? Why does nobody know that?”

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Dog cancer research is helping drug development for humans and canines

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