Open AccessTKI258 Is Efficacious as a Multitargeted TKI in Head and Neck Squamous Cell Carcinoma Models
Author(s) -
Sweeny Larissa,
Hartman Yolanda,
Liu Zhiyong,
Rosenthal Eben L.,
Knowles Joseph
Publication year - 2011
Publication title -
otolaryngology–head and neck surgery
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.232
H-Index - 121
eISSN - 1097-6817
pISSN - 0194-5998
DOI - 10.1177/0194599811416318a115
Subject(s) - head and neck squamous cell carcinoma , cell growth , apoptosis , cancer research , cell culture , in vivo , platelet derived growth factor receptor , cell , cytotoxicity , growth inhibition , tyrosine kinase inhibitor , medicine , in vitro , receptor , biology , cancer , growth factor , head and neck cancer , biochemistry , genetics , microbiology and biotechnology
Objective Dovitinib (TKI28) is a multitargeted tyrosine kinase inhibitor that has not been previously investigated in the pre‐clinical setting for the treatment of head and neck squamous cell carcinoma (HNSCC). Dovitinib is administered orally and targets receptors (FGFR1/2/3 and PDGF‐beta) known to promote cell survival and proliferation and decrease cell apoptosis. Method HNSCC cell lines and human tumor samples were evaluated for FGFR1/2/3, and PDGF‐beta expression levels. Cell lines (FADU, SCC1, OSC19, Cal27, SCC22A) were treated with a range of physiological concentrations of dovitinib and assessed for proliferation, cytotoxicity, and apoptosis. Mice bearing HNSCC xenografts were treated with dovitinib (20 mg/kg). Results Elevated expression of FGFR2, FGFR3, and PDGF‐beta were indentified in HNSCC cell lines and human tumor specimens. In vitro, dovitinib reduced HNSCC cell proliferation (40‐80%) and viability (40‐60%). In a dose‐dependent fashion, dovitinib also induced cytotoxicity and apoptosis in HNSCC cell lines. When co‐cultured with fibroblasts, HNSCC cells proliferation was also decreased by dovitinib. In vivo, oral administration of dovitinib resulted in significant tumor regression and growth inhibition (67%). Disease‐free survival at 75 days following completion of treatment was 33% and stable disease occurred in another 33%. Conclusion This is the first report to demonstrate dovitinib inhibits HNSCC cell growth in vitro and in vivo.