PMC:3730145 / 15913-17890 JSONTXT

{"project":"2_test","denotations":[{"id":"23970998-19641938-82904835","span":{"begin":458,"end":460},"obj":"19641938"},{"id":"23970998-16763281-82904836","span":{"begin":462,"end":464},"obj":"16763281"},{"id":"23970998-19641938-82904837","span":{"begin":797,"end":799},"obj":"19641938"},{"id":"23970998-19754827-82904838","span":{"begin":870,"end":872},"obj":"19754827"},{"id":"23970998-23106467-82904838","span":{"begin":870,"end":872},"obj":"23106467"},{"id":"23970998-21569196-82904838","span":{"begin":870,"end":872},"obj":"21569196"},{"id":"23970998-23106467-82904839","span":{"begin":1027,"end":1029},"obj":"23106467"},{"id":"23970998-21569196-82904840","span":{"begin":1031,"end":1033},"obj":"21569196"},{"id":"23970998-21464610-82904841","span":{"begin":1359,"end":1361},"obj":"21464610"},{"id":"23970998-22342216-82904842","span":{"begin":1609,"end":1611},"obj":"22342216"},{"id":"23970998-21464610-82904843","span":{"begin":1787,"end":1789},"obj":"21464610"},{"id":"23970998-22342216-82904844","span":{"begin":1791,"end":1793},"obj":"22342216"},{"id":"23970998-21464610-82904845","span":{"begin":1973,"end":1975},"obj":"21464610"},{"id":"T40895","span":{"begin":458,"end":460},"obj":"19641938"},{"id":"T66170","span":{"begin":462,"end":464},"obj":"16763281"},{"id":"T89970","span":{"begin":797,"end":799},"obj":"19641938"},{"id":"T33222","span":{"begin":870,"end":872},"obj":"19754827"},{"id":"T45906","span":{"begin":870,"end":872},"obj":"23106467"},{"id":"T2058","span":{"begin":870,"end":872},"obj":"21569196"},{"id":"T3782","span":{"begin":1027,"end":1029},"obj":"23106467"},{"id":"T66003","span":{"begin":1031,"end":1033},"obj":"21569196"},{"id":"T18993","span":{"begin":1359,"end":1361},"obj":"21464610"},{"id":"T92713","span":{"begin":1609,"end":1611},"obj":"22342216"},{"id":"T76288","span":{"begin":1787,"end":1789},"obj":"21464610"},{"id":"T26268","span":{"begin":1791,"end":1793},"obj":"22342216"},{"id":"T103","span":{"begin":1973,"end":1975},"obj":"21464610"}],"text":"2.4.1. Epidermal Growth Factor Receptor\nThe epidermal growth factor receptor (EGFR) signaling pathway has been implicated in the oncogenesis of HNSCC. Epidermal growth factor receptor is a transmembrane receptor tyrosine kinase that controls cellular pathways crucial in cancer development, growth, invasion, metastasis, and angiogenesis. Up to 90% of HNSCC exhibit overexpression of EGFR, which is prognostic for overall survival and disease-free interval [37, 45]. EGFR-targeted therapies have been explored, with blocking of EGFR resulting in inhibition of cell proliferation, enhancement of apoptosis, and reduction in the metastatic and angiogenic potential of HNSCC. In addition, monoclonal antibodies (e.g., cetuximab) have been investigated in clinical HNSCC patients with modest results [37]. \nIn cats with FOSCC, EGFR is similarly highly expressed (69%–100%) [46–48]. The significance of EGFR tumor expression is unclear, with two studies demonstrating either high or low EGFR scores associated with better survival [47, 48]. Limitations in comparison of these studies as well as comparison to human studies include the retrospective nature, small sample size, variability in patient treatment, and variability in method of EGFR scoring and cellular localization. In vitro in feline cells, EGFR has been associated with proliferation and migration [49]. A population of putative cancer stem cells with enhanced sphere-forming ability, reduced sensitivity to radiation and conventional chemotherapy, and demonstrated resistance to gefitinib (EGFR-targeting drug) has also been demonstrated in FOSCC [50]. Gefitinib results in reduced cell proliferation and migration as well as a change in cell morphology and gene expression suggestive of epithelial to mesenchymal transition [49, 50]. EGFR-targeting with RNAi resulted in reduction in EGFR activity, reversal of acquired gefitinib resistance, and an additive effect on cell killing when combined with radiation [49]."}