Introduction
We previously demonstrated hyperactivation of the MAPK pathway in canine oral squamous cell carcinomas (OSCCs) and showed that trametinib blocks growth of culture and xenograft models. Here, we tested whether trametinib could reduce tumor volume in dogs with OSCC and thus qualify as a candidate neoadjuvant intervention.

Materials and Methods
 A total of 16 client-owned adult dogs with OSCC, no evidence of metastasis and no previous excision or radiation therapy, were enrolled in a 2-month clinical trial. Dogs received daily oral trametinib (0.015 - 0.03 mg/kg). Tumor volume was measured using contrast-enhanced computed tomography (CT) at days 0, ~30, and ~60, and compared. Dogs that exhibited continued tumor growth exited the study. Potential side effects were monitored biweekly with a physical exam, routine bloodwork and a toxicity questionnaire.

Results
Tumor volume reduction was achieved in 7 dogs (43.75%), with a median volume percentage change of 41.3%. Tumor volume remained static or exhibited continued growth in 9 dogs (56.25%) with a median percentage change of 153.1%. Response to trametinib was not associated with initial tumor volume, body weight, sex or age. All dogs tolerated trametinib with no side effects observed or reported during the trial.

Conclusions
Trametinib can significantly reduce tumor volume in more than 40% of dogs with OSCC without metastatic disease and is well tolerated. Future studies will help identify which subsets of dogs with OSCC are more likely to benefit from neoadjuvant trametinib.