Studies on the inhibition of feline EGFR in squamous cell carcinoma: enhancement of radiosensitivity and rescue of resistance to small molecule inhibitors

Bergkvist, G. T., Argyle, D. J., Pang, L. Y., Muirhead, R. and Yool, D. A. (2011) Studies on the inhibition of feline EGFR in squamous cell carcinoma: enhancement of radiosensitivity and rescue of resistance to small molecule inhibitors. Cancer Biology and Therapy, 11(11), pp. 927-937. (doi: 10.4161/cbt.11.11.15525) (PMID:21464610)

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Abstract

This study investigated different methods of EGFR (Epithelial Growth Factor Receptor) targeting in feline squamous cell carcinoma with the ultimate aim of establishing a large animal model of human head and neck cancer. Both small molecule receptor tyrosine kinase inhibitor (TKI) and RNA interference (RNAi) techniques were employed to target the feline EGFR. We demonstrated that the human drug gefitinib caused a reduction in cell proliferation and migration in a feline cell line. However, we also document the development of resistance that was not associated with mutation in the kinase domain. RNAi caused a potent reduction in EGFR activity and was able to overcome acquired gefitinib resistance. In addition, RNAi targeting of EGFR, but not gefitinib, caused an additive effect on cell killing when combined with radiation. These results support the use of feline SCC as a model of head and neck cancer in man in the search for novel and effective treatments for both tumors.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Yool, Professor Donald
Authors: Bergkvist, G. T., Argyle, D. J., Pang, L. Y., Muirhead, R., and Yool, D. A.
College/School:College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
Journal Name:Cancer Biology and Therapy
Publisher:Taylor and Francis
ISSN:1538-4047
ISSN (Online):1555-8576

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