Enlisting A Dog In The Fight Against Cancer

Cheryl London, DVM, PhD, The Ohio State University College of Veterinary MedicineCheryl London, DVM, PhD, The Ohio State University College of Veterinary MedicineFor years, dogs have sniffed-out land mines, rescued earthquake victims, and guided the blind. Today our BFFs are teaming up with us to confront a shared formidable foe — cancer.

America’s 83 million pet dogs share our environment, have similar genomes and develop spontaneous tumors much like we do. Researchers say opportunities for specialists in canine and human oncology to work together to develop mutually beneficial, more effective and less toxic anti-cancer drugs for both species are boundless. The challenge is on.

Scientists, physicians, veterinarians, National Cancer Institute and industry representatives gathered at Duke in February for the second annual symposium of the Consortium for Canine Comparative Oncology (C3O) — a collaborative research partnership between Duke Cancer Institute and North Carolina State University College of Veterinary Medicine — to share how they’re advancing care and prevention.

They drilled down on the particular possibilities in immuno-oncology.

“Certainly, it’s not lost on us that the pharmaceutical and biotech industry has identified immunotherapy as the latest and greatest new approach to treating cancer, but it’s very challenging to get all the answers that we need for developing new immunotherapies using human patients,” said executive director of DCI Michael Kastan, MD, PhD, a consortium co-founder. “We think there are particular opportunities for testing these reagents in canine patients which can be done more quickly than human trials and at a fraction of the cost.”

He pointed out that while cancer in dogs tends to be a little more aggressive than in humans, canine tumors have similar imaging and treatment modalities, metastasis and recurrence patterns, latency periods, and potentially the same causation. Cancer is the leading cause of death in dogs, with one in four developing the disease in his or her lifetime. For humans, it’s one in three.

Keynote speaker Cheryl London, DVM, PhD, a canine oncology researcher and professor at The Ohio State University College of Veterinary Medicine, reminded participants that “the notion of using dogs for translational work is not new,” nor is “helping the human side by leveraging cancer in dogs in the setting of immunotherapy,” but she’s encouraged that her life’s work and the work of many others is getting more publicity now.  

On the Scent of Discovery

The leaders of four canine comparative oncology pilot projects — awarded up to $100K per project last year by the consortium, with the added support of the V Foundation and Genentech — presented progress reports on their breakthrough research.

Ashutosh Chilkoti, PhD (a DCI member and chair of the Department of Biomedical Engineering at Duke) and NC State’s Steven Suter, PhD, were awarded funding for their project, “A Phase 1 Clinical Trial of CP-DOX in Dogs: A Novel Nanoparticle Formation of an Old Drug,” for treating dogs with high-grade B-cell lymphoma.   Rodney Page, DVM, MS, Colorado State University (left), Michael B. Kastan, MD, PhD, Duke Cancer Institute (right) Rodney Page, DVM, MS, Colorado State University (left), Michael B. Kastan, MD, PhD, Duke Cancer Institute (right)

“One of the reasons that this application generated a lot of enthusiasm with the review committee was because it’s a wonderful example of how this partnership can more rapidly advance the development of novel drugs,” said Kastan. “When we see the data from the clinical trial, it will greatly facilitate our ability to take this to humans.”

William Eward, DVM, MD, an orthopedic surgeon with DCI and veterinarian, works to find better treatments for sarcoma in dogs and humans. He and his N.C. State research partner Matthew Breen, PhD, were awarded funding as co-principal investigators for two sarcoma-related pilot projects.

Eward said a lack of advance in treatments for human sarcomas, a relatively uncommon cancer, has primarily been due to the lack of access to patient samples and very limited studies of such cases. There are thousands more sarcoma cases in dogs.

Eward and Breen are conducting cross-species genomic analysis and drug screening, utilizing a mouse-to-dog-to-human platform that they believe is “one-of-its-kind.”

“Not only are we the only place that I know of that has canine PDx , we have this whole pathway than can take sarcomas from either species and test them from cells to patients,” said Eward. “This is a strong collaboration and getting stronger thanks to this C30 funding. We’ve been able to go from talking about things we would like to do to actually getting in gear and doing it.”

Breen and DCI surgical oncologist Brant Inman, MD, MS, meanwhile, were funded for their work examining whether environmental influences genetically affect people and dogs similarly; particularly in the development of bladder cancer, a highly mutated cancer that’s extremely responsive to immunotherapies.

They are sequencing bladder cancer genomes in dogs and humans and looking for carcinogen-induced mutational signatures. The team is currently working on sequencing six specific mutagens found in the environment — in tobacco, pesticides and water.

Other symposium highlights included advances in immunotherapy for brain tumors and implications for dogs (DCI-John Sampson, MD, PhD, MHSc, MBA); human B cell immunotherapies and the potential for “canine-izing” them (DCI-Thomas Tedder, PhD); PD-L1 expression and signaling by tumors and myeloid cells in mice vs. dogs (Colorado State University-Steven Dow, DVM, PhD); and the development of a DNA vaccine for melanoma and other spontaneous cancers in dogs (Philip Bergman, DVM, MS, PhD, VCA Clinical Studies). 

Bonafide Buy-In

Symposium participants agreed that, moving forward, the vital scientific work of the consortium would only be sustainable and expandable with next-level education and engagement of pharma, biotech, government, foundations and philanthropy.

“The reason we are funding this innovative research is not only for its product but because of the hope that it will represent a bridge to new competitive funding,” said dean of the College of Veterinary Medicine at NC State Paul Lunn, BVSc, MS, PhD, MRCVS, and consortium co-founder.

Mark Dewhirst, DVM, PhD, vice director for basic science at Duke Cancer Institute, whose been involved in the canine comparative oncology field for most of his 35-year career, said he was pleased that this year’s symposium got “more granular” about the canine model and forced the group to consider how best to advance and market that model to the greater oncology community.

Tom Ribar, Duke Cancer Institute (middle), and Kristy Richards, Md, PhD, Cornell University (at right)  at the poster session portion of the symposium.Tom Ribar, Duke Cancer Institute (middle), and Kristy Richards, Md, PhD, Cornell University (at right) at the poster session portion of the symposium.According to Dewhirst, many cancer patients are already sold on the idea of how they and their pets can be helped by this collaborative research.

“I think the cancer patients who know about it and know what it can offer are really very encouraged by what we can do,” he said. “I’ve had many clients in my career who were both cancer survivors and had pets with cancer and they truly understood what the pets could do to help them and other people with that same disease.”

The second annual Joint Institution Funding Opportunity, up to $100K per project, is being offered for pilot projects in canine comparative oncology that will translate laboratory discoveries into diagnostic, prognostic, or therapeutic applications. The submission deadline of May 1.  To learn more, visit C3O.

“The Answer to Cancer May Be Walking Right Beside Us,” a documentary produced by Colorado State University and Rocky Mountain PBS, will air nationally on public television stations starting in April 2017. The documentary features CSU's Rodney Page, DVM, MS, and DCI's Michael B. Kastan, MD, PhD, among other researchers. Consult your local listings to find the air date and watch the trailer for the documentary.