title: Studies on the inhibition of feline EGFR in squamous cell carcinoma: enhancement of radiosensitivity and rescue of resistance to small molecule inhibitors.
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.
authors.affiliation: Royal (Dick) School of Veterinary Studies and The Roslin Institute, Division of Veterinary Clinical Sciences, The University of Edinburgh, Easter Bush Veterinary Centre, Roslin, Midlothian, UK. Gura.Bergkvist@ed.ac.uk
authors.forename: Gurå T
authors.initials: GT
authors.lastname: Bergkvist
authors.forename: David J
authors.initials: DJ
authors.lastname: Argyle
authors.forename: Lisa Y
authors.initials: LY
authors.lastname: Pang
authors.forename: Rhona
authors.initials: R
authors.lastname: Muirhead
authors.forename: Donald A
authors.initials: DA
authors.lastname: Yool
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000532:radiotherapy; D002415:Cats; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003131:Combined Modality Therapy; D017124:Conserved Sequence; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics; D000077156:Gefitinib; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D006801:Humans; D011799:Quinazolines / Q000494:pharmacology*; D034622:RNA Interference; D011836:Radiation Tolerance / Q000235:genetics*; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib