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Could an MEK inhibitor prevent dogs with oral squamous cell carcinoma from needing surgery? William Katt, PhD, a senior research associate at Cornell, and Santiago Peralta, DVM, DAVDC, an associate professor at Cornell, served as corresponding authors on a study looking at this topic. Trametinib is an MEK inhibitor that is FDA-approved for many indications in humans, one of which is melanoma. In this study, researchers evaluated the cell lines of canine oral squamous cell carcinoma, tested various therapeutic and chemotherapeutic agents including trametinib via animal-derived cell culture models, and piloted a clinical trial to assess how trametinib can debulk canine oral squamous cell carcinoma tumors.
In this interview, Dr. Katt discusses the preliminary results, some of the challenges associated with conducting clinical trials in veterinary medicine, and the potential clinical impact from this work.
What do you think is the biggest breakthrough from this study?
Dr. Katt: The key take-home message is that this FDA-approved molecule can be repurposed to target oral squamous cell carcinoma in dogs. This is a deadly disease with a very aggressive standard of care treatment (surgery) currently, so any advances could help a lot of dogs.
What could be the future clinical impact of this early clinical data?
Dr. Katt: In the immediate future, what we’re hoping is that this drug will be adopted into the standard of care to help shrink a tumor before surgery. In the longer term? We’d love to see a purely chemical approach to managing the disease and eliminating surgery entirely.
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If this study is a launching point, what should future studies focus on?
Dr. Katt: The most obvious place to start is to stratify patients. Our ongoing clinical trial has continued to have a roughly 50% success rate for the drug in shrinking tumors. What we really want to do now is figure out what the responsive patients have in common so that we know which dogs should be prescribed this drug and which should go straight to the current standard of care.
Do you foresee future studies using trametinib for other canine cancers (i.e., it has been used off-label to treat canine histiocytic sarcoma)?
Dr. Katt: We absolutely imagine trametinib could be used for other canine cancers. MEK activation is part of the RAS pathway, which is one of the most commonly activated pathways in all cancers. While our own focus is oral tumors, we are also aware of those trials for histiocytic sarcoma and imagine other tumors might be responsive as well. As in so much of science, the major bottlenecks are time and money. It’s only ethical to conduct experiments on live animals once everything possible has been done to show that a treatment is likely to work on model systems of the disease. For dogs, those model systems are very difficult to come by and take a lot of time and money to develop.
What did you find most promising about the treatment of trametinib for canine oral squamous cell carcinoma?
Dr. Katt: Honestly, we were absolutely blown away by just how effective the drug was in some patients. We went into this thinking we might slow down tumor growth or maybe shrink it a little bit. Instead, for some of the most responsive patients, we’re seeing the tumor totally vanish, accompanied by regrowth of nearby bone. When you couple that with how safe the drug has been shown to be and how affordable it is, we really think that this could become a part of the standard of care for some patients.
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What is the biggest limitation of this study?
Dr. Katt: Numbers. 100%, it’s the number of patients we’ve seen. With 4 patients, we couldn’t draw any statistically significant conclusions. And even in our more complete clinical study that we’re writing up right now, the sad fact is that the numbers are just very small. When you look at clinical trials in humans, they examine thousands of people; and they correlate data across gender, ethnic group, age, and every other factor they can think of. And we don’t have the ability to do that right now. So, while we do think our data is meaningful, it is really important to remember that the statistical power of the study is limited; and we’ll only be able to divide the patient population into so-fine groups.
The Study
The MEK inhibitor trametinib is effective in inhibiting the growth of canine oral squamous cell carcinoma.
Katt WP, Balkman CE, Butler SD, et al. Sci Rep.
https://doi.org/10.1038/s41598-025-90574-3