Comprehensive kinase inhibitor screening reveals potential therapeutic targets in canine melanoma: A Comparative Precision Oncology study

Melanoma is a highly aggressive cancer in both humans and dogs with significant biological and clinical similarities. This study aimed to identify therapeutic kinase targets in canine melanoma by screening kinase inhibitors in canine melanoma cell lines. Cell viability assays showed that seven inhibitors reduced viability in both CMGD2 and TLM1 cells, whereas additional compounds showed cell line-specific activity. The most promising kinase targets were AURKA, AURKB, AXL, CLK1/2/4, IGF1R, MAP2K1, and MAP2K2. Gene expression analysis confirmed expression of these targets in the cell lines, except for CLK3. In silico analyses revealed high structural homology (≥90%) between canine and human kinases, supporting the translational relevance of these findings. Molecular docking further demonstrated similar predicted binding profiles between human and canine kinases. Several FDA-approved drugs targeting these kinases were identified as potential repurposing candidates for canine melanoma treatment. These findings highlight the potential of targeted therapies for canine melanoma and reinforce the value of comparative oncology in advancing precision medicine across species. However, these findings are based on an exploratory single-dose in vitro screen, a small tumor cohort, and in silico analyses, and therefore require dose-response, protein-level, and in vivo validation.