Winn grant W11-027
Cetuximab Targeting of Epidermal Growth Factor Receptor in Feline Oral Squamous Cell Carcinoma
Investigators: Stuart Helfand and Krystal Claybrook; Oregon State University
|Elderly cats are most at risk for oral cancer|
Feline oral squamous cell carcinoma (FOSCC) is a common and deadly cancer for which there are no truly effective therapies. This study’s long-term aim is to suppress growth of FOSCC by interrupting signaling through the epidermal growth factor receptor (EGFR). EGFR-signaling is a known trigger for cell growth making it a desirable target for therapy. The study considers two strategies of interest that share the same goal of impeding EGFR signaling. One method is to use cetuximab for monoclonal antibody blockade of the receptor. The alternate method is use of tyrosine kinase inhibitor (TKI) blockade of the receptor’s activation site. The impairment of signaling suppresses a number of processes that would otherwise promote malignant behavior.
Previous study results showed EGFR is expressed by the only cell line of FOSCC available and that cetuximab can bind to FOSCC biopsy tissue. Despite the prior data, this investigator unexpectedly discovered that cetuximab did not bind to the cells. The study then turned to pursuing the alternate approach to block EGFR signaling by examining a TKI drug, gefitinib, on proliferation of this cell line. Results in this instance confirmed the ability to interrupt EGFR signaling in the cell line by using gefitinib, resulting in suppression of the tumor cells. Data has indicated that this approach is effective and may facilitate use of lower drug doses while achieving superior cell killing.
Additional time is needed to confirm the results and validate targeting of gefitinib (and another TKI drug, dasatinib) to EGFR by western blot analysis. [VT]