Preliminary studies have supported use of
toceranib phosphate (Palladia®) in treatment of canine nasal
carcinomas, though the mechanisms of its activity are unknown. This study evaluated sixteen canine nasal
carcinoma and five normal nasal epithelium samples for expression and phosphorylation of known targets of toceranib [
vascular endothelial growth factor receptor-2 (VEGR2),
platelet derived growth factor alpha (PDGFR-α),
platelet derived growth factor receptor beta (PDGFR-β), and
stem cell factor receptor (c-KIT)] and
epidermal growth factor receptor 1 (EGFR1) using immunohistochemistry, RT-PCR and a
receptor tyrosine kinase (RTK) phosphorylation panel.
Protein for VEGFR2 was expressed in all
carcinomas, PDGFR-α was noted in 15/16, whereas PDGFR-β was detected in 3/16 samples, but showed significant stromal staining.
Protein expression for c-KIT was present in 4/16 and EGFR1 was noted in 14/16 samples. Normal tissue showed variable
protein expression of the RTKs.
Messenger RNA for VEGFR2, PDGFR-β, and c-KIT were noted in all samples.
Messenger RNA for PDGFR-α and EGFR1 were detected in 15/16 samples. All normal nasal tissue detected
messenger RNA. Phosphorylation of VEGFR2, PDGFR-α, PDGFR-β and c-KIT was not observed in any
carcinoma or normal nasal sample, but phosphorylation of EGFR1 was noted in 10/16
carcinoma and 3/5 normal samples. The absence of phosphorylated RTK targets of toceranib suggests any clinical effect of toceranib occurs through inhibition of alternative unidentified RTK pathways in canine nasal
carcinomas. The observed
protein and message expression and phosphorylation of EGFR1 in the nasal
carcinoma samples merits further inquiry into EGFR1 as a therapeutic target for this
cancer.