A research study on oral squamous cell carcinoma (OSCC) in dogs is enrolling patients at the Cornell University Hospital for Animals (CUHA) to test a new drug treatment for this aggressive type of cancer. OSCC is among the most frequently diagnosed malignant tumors in dogs and can invade tissues deeply, destroying teeth, soft tissues and jawbones as well as spreading to other organs.

“Currently, if we catch the cancer on time, we can treat it surgically, but surgery is invasive, expensive, complex, and often leaves a very dysfunctional patient, with a large portion of the animal’s jaw removed,” said Dr. Santiago Peralta, associate professor in the section of dentistry and oral surgery of the Department of Clinical Sciences at Cornell University College of Veterinary Medicine (CVM), and one of the principal investigators (PIs) of the study.

Many owners reject the treatment because it can lead to additional medical issues and reduces their pet’s quality of life. “But if we can show our new treatment works, it will give clinicians across the country and across the world a better treatment option for a cancer that is normally highly disfiguring,” said co-PI Dr. William Katt, senior research associate in the Department of Molecular Medicine at CVM.

The therapy under investigation consists of an oral course of trametinib, a drug the researchers hope will shrink the tumor. They are building on several years of research and collaboration – funded, like the current work, by the Cornell Richard P. Riney Canine Health Center – during which they have studied the molecular mechanisms underlying tumor formation. Extensive genomic profiling of canine OSCCs showed that an important cellular mechanism known as RAS signaling becomes abnormally activated and triggers tumor growth.

“This allowed us to postulate some hypotheses, including wondering whether there were some drugs that could be used to treat these tumors,” Peralta recounted. The team chose to focus on the drug trametinib, which blocks the protein MEK, thereby inhibiting its key signaling partner, the enzyme RAS, from telling cancer cells to grow uncontrollably. And indeed, controlled laboratory experiments – using disease models created by Katt – showed that this drug was effective in stopping the growth of OSCC cells.

“So all this infrastructure we've been creating and working really hard on for several years now is starting to come full circle,” Peralta said. “After developing models and doing numerous drug experiments, we are comfortable enough to bring this promising drug to clinical trial.”

The researchers have reason to be optimistic. Trametinib is already FDA-approved for treatment of metastatic melanomas in humans, and experimental tests in dogs have determined safe doses. “There’s already a tremendous amount of safety data out there for this molecule, so we’re really confident that this is at the very least not going to harm the dog,” Katt said.

Now their work will help to determine an effective dose in dogs with natural disease, and they will run molecular assays to identify genetic markers of tumors that are more likely to respond to therapy. In fact, positive outcomes may have even greater implications. “The tumors may be similar enough to human counterparts that at some point they could, potentially, be used to inform interventions in people,” Peralta said.

The current study began last year and will be actively enrolling up to 25 dogs. Participants will receive the regular standard of care for OSCC, plus the test drug. The costs of the medication and medical interventions – outside of any surgery – will be subsidized for the participating dogs.

Once a patient is enrolled, the veterinarians use pathology of tissue samples and a CT scan to determine the size and extent of local disease and whether it has spread to other parts of the body. If the disease is still localized – as is typically the case – and the dog is a good candidate, surgery is scheduled for a few weeks later. In the meantime, the dogs receive a daily oral capsule of trametinib.

“We are closely monitoring the tumor to see whether it shrinks,” Peralta explained. “Ideally it will disappear at some point, although that may be wishful thinking. But we are hoping that we can at least reduce the size enough to allow less detrimental surgery later on.” If the tumor does not stop growing, the dog will be removed from the study and continue to surgery immediately at the owner’s request.

The results thus far have been promising. “We achieved fifty percent or more reduction in tumor volume in two of the dogs enrolled so far, which is truly remarkable,” Peralta said. “And in the four dogs we have enrolled to date, we have seen no toxicity whatsoever. So, very early during the trial, we are already seeing very encouraging things. We’re very excited.”

Rory Todhunter, Ph.D. '92, director of the Cornell Richard P. Riney Canine Health Center, the center funding the research, added, “The center has two main research goals that will enhance the health and longevity of dogs – to provide substantial and ongoing research funding to discover novel interventions to help dogs with any disease, and to make sure that the dog-loving public know and understand the importance of this research and what we are doing in the laboratory and in subsequent clinical trials. I applaud Santiago. His research is a perfect example of how the Riney Canine Health Center supports basic science which can be translated in to clinical practice quickly.”

Additionally, this research brings together facilities and collaborative use of  resources across the College of Veterinary Medicine and the University, including the sections of dentistry and oral surgery, oncology, and diagnostic imaging; the clinical trials coordination group at CUHA; Progressive Assessment of Therapeutics (PATh) PDX Facility; DCS Innovation Lab; Transcriptional Regulation and Expression Facility; Cornell Vetarinary Biobank; Animal Health and Diagnostic Center; and the labs of Goldwin Smith Professor of Pharmacology and Chemical Biology Dr. Richard Cerione and associate profesor of biomedical sciences  Dr. Andrew White.

For more information and to enroll your dog in the trial, please visit the study website.

Dr. Peralta will also hold a webinar on the study for regional veterinarians on Thursday, February 29, 2024 at 6 PM.

View the webinar recording here. 

Written by Olivia M. Hall