A1 Refereed original research article in a scientific journal
The MEK inhibitor trametinib is effective in inhibiting the growth of canine oral squamous cell carcinoma
Authors: Katt W.P., Balkman C.E., Butler S.D., Byron M., Carney P.C., Todd-Donato A.B., Drozd M.E., Duhamel G.E., Evans J.M., Fiani N., Ford J.C., Grenier J.K., Hayward J.J., Heikinheimo K., Hume K.R., Moore E.S., Puri R., Sylvester S.R., Warshaw S.L., Webb S.M., White A.C., Wright A.L., Cerione R.A., Peralta S.
Publisher: Springer Nature
Publication year: 2025
Journal: Scientific Reports
Journal name in source: Scientific Reports
Article number: 7069
Volume: 15
eISSN: 2045-2322
DOI: https://doi.org/10.1038/s41598-025-90574-3(external)
Web address : https://www.nature.com/articles/s41598-025-90574-3(external)
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/491567848(external)
Oral tumors are relatively common in dogs, and canine oral squamous cell carcinoma (COSCC) is the most prevalent oral malignancy of epithelial origin. COSCC is locally aggressive with up to 20% of patients showing regional or distant metastasis at the time of diagnosis. The treatment of choice most typically involves wide surgical excision. Although long-term remission is possible, treatments are associated with considerable morbidity and can negatively impact functionality and quality of life. OSCCs have substantial upregulation of the RAS-RAF-MEK-MAPK signaling axis, and we had previously hypothesized that small-molecule inhibitors that target RAS signaling might effectively inhibit tumor growth and progression. Here, we demonstrate that the MEK inhibitor trametinib, an FDA-approved drug for human cancers, substantially inhibits the growth of six COSCC cell lines established from current patient tumor samples. We further show preliminary clinical evidence that the drug is able to cause ~ 40% and ~ 80% tumor regression in two out of four patients with spontaneously occurring COSCC, a partial response according to commonly used RECIST criteria. Given the limited treatment options available and the number of dogs for which standard of care is not acceptable, these preliminary findings provide new hope that more suitable treatment options may soon enter the veterinary clinic.
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Funding information in the publication:
We would like to acknowledge funding from the Cornell Richard P. Riney Canine Health Center to WPK and SP, from the National Cancer Institute (5R01CA201402-09) to RAC, and from the Maritza and Reino Salonen Foundation to KH. Biological material and associated data were provided by the Cornell Veterinary Biobank, a resource built with the support of NIH grant R24 GM082910 and the Cornell University College of Veterinary Medicine, and by the Cornell Animal Health Diagnostic Center.
