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.

journal_name

Cancer Biol Ther

journal_title

Cancer biology & therapy

authors

Bergkvist GT,Argyle DJ,Pang LY,Muirhead R,Yool DA

doi

10.4161/cbt.11.11.15525

subject

Has Abstract

pub_date

2011-06-01 00:00:00

pages

927-37

issue

11

eissn

1538-4047

issn

1555-8576

pii

15525

journal_volume

11

pub_type

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