The MEK inhibitor trametinib is effective in inhibiting the growth of canine oral squamous cell carcinoma
Abstract 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 cho...
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2025-02-01
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| Online Access: | https://doi.org/10.1038/s41598-025-90574-3 |
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| author | William P. Katt Cheryl E. Balkman Scott D. Butler Michael Byron Patrick C. Carney Amy B. Todd-Donato Matthew E. Drozd Gerald E. Duhamel Jacquelyn M. Evans Nadine Fiani Jordan C. Ford Jennifer K. Grenier Jessica J. Hayward Kristiina Heikinheimo Kelly R. Hume Elizabeth S. Moore Rishi Puri Skylar R. Sylvester Sydney L. Warshaw Suzin M. Webb Andrew C. White Alexandra L. Wright Richard A. Cerione Santiago Peralta |
| author_facet | William P. Katt Cheryl E. Balkman Scott D. Butler Michael Byron Patrick C. Carney Amy B. Todd-Donato Matthew E. Drozd Gerald E. Duhamel Jacquelyn M. Evans Nadine Fiani Jordan C. Ford Jennifer K. Grenier Jessica J. Hayward Kristiina Heikinheimo Kelly R. Hume Elizabeth S. Moore Rishi Puri Skylar R. Sylvester Sydney L. Warshaw Suzin M. Webb Andrew C. White Alexandra L. Wright Richard A. Cerione Santiago Peralta |
| author_sort | William P. Katt |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-4f9065e06f0c403dbfcdf12c73bc500a |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-4f9065e06f0c403dbfcdf12c73bc500a2025-08-20T03:04:16ZengNature PortfolioScientific Reports2045-23222025-02-0115111910.1038/s41598-025-90574-3The MEK inhibitor trametinib is effective in inhibiting the growth of canine oral squamous cell carcinomaWilliam P. Katt0Cheryl E. Balkman1Scott D. Butler2Michael Byron3Patrick C. Carney4Amy B. Todd-Donato5Matthew E. Drozd6Gerald E. Duhamel7Jacquelyn M. Evans8Nadine Fiani9Jordan C. Ford10Jennifer K. Grenier11Jessica J. Hayward12Kristiina Heikinheimo13Kelly R. Hume14Elizabeth S. Moore15Rishi Puri16Skylar R. Sylvester17Sydney L. Warshaw18Suzin M. Webb19Andrew C. White20Alexandra L. Wright21Richard A. Cerione22Santiago Peralta23Department of Molecular Medicine, Cornell UniversityDepartment of Clinical Sciences, Cornell UniversityDepartment of Biomedical Sciences, Cornell UniversityDepartment of Clinical Sciences, Cornell UniversityDepartment of Clinical Sciences, Cornell UniversityDepartment of Clinical Sciences, Cornell UniversityDepartment of Clinical Sciences, Cornell UniversityDepartment of Biomedical Sciences, Cornell UniversityDepartment of Biomedical Sciences, Cornell UniversityDepartment of Clinical Sciences, Cornell UniversityGenomics Facility, Institute of Biotechnology, Cornell UniversityGenomics Facility, Institute of Biotechnology, Cornell UniversityDepartment of Biomedical Sciences, Cornell UniversityDepartment of Oral and Maxillofacial Surgery, Institute of Dentistry, University of Turku and Turku University HospitalDepartment of Clinical Sciences, Cornell UniversityDepartment of Biomedical Sciences, Cornell UniversityDepartment of Biomedical Sciences, Cornell UniversityDepartment of Biomedical Sciences, Cornell UniversityPrism Veterinary DentistryDepartment of Clinical Sciences, Cornell UniversityDepartment of Biomedical Sciences, Cornell UniversityDepartment of Clinical Sciences, Cornell UniversityDepartment of Molecular Medicine, Cornell UniversityDepartment of Clinical Sciences, Cornell UniversityAbstract 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.https://doi.org/10.1038/s41598-025-90574-3Oral squamous cell carcinomaCanine cancerTrametinibRAS signaling |
| spellingShingle | William P. Katt Cheryl E. Balkman Scott D. Butler Michael Byron Patrick C. Carney Amy B. Todd-Donato Matthew E. Drozd Gerald E. Duhamel Jacquelyn M. Evans Nadine Fiani Jordan C. Ford Jennifer K. Grenier Jessica J. Hayward Kristiina Heikinheimo Kelly R. Hume Elizabeth S. Moore Rishi Puri Skylar R. Sylvester Sydney L. Warshaw Suzin M. Webb Andrew C. White Alexandra L. Wright Richard A. Cerione Santiago Peralta The MEK inhibitor trametinib is effective in inhibiting the growth of canine oral squamous cell carcinoma Scientific Reports Oral squamous cell carcinoma Canine cancer Trametinib RAS signaling |
| title | The MEK inhibitor trametinib is effective in inhibiting the growth of canine oral squamous cell carcinoma |
| title_full | The MEK inhibitor trametinib is effective in inhibiting the growth of canine oral squamous cell carcinoma |
| title_fullStr | The MEK inhibitor trametinib is effective in inhibiting the growth of canine oral squamous cell carcinoma |
| title_full_unstemmed | The MEK inhibitor trametinib is effective in inhibiting the growth of canine oral squamous cell carcinoma |
| title_short | The MEK inhibitor trametinib is effective in inhibiting the growth of canine oral squamous cell carcinoma |
| title_sort | mek inhibitor trametinib is effective in inhibiting the growth of canine oral squamous cell carcinoma |
| topic | Oral squamous cell carcinoma Canine cancer Trametinib RAS signaling |
| url | https://doi.org/10.1038/s41598-025-90574-3 |
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