Combination of phosphotidylinositol-3-kinase targeting with cetuximab and irradiation: A preclinical study on an orthotopic xenograft model of head and neck cancer
Corresponding Author
Alexandre Bozec MD, PhD
University Institute of the Face and Neck, Nice cedex, France
Corresponding author: A. Bozec, University Institute of the Face and Neck, 31 avenue de Valombrose, 06103 Nice, France. E-mail: [email protected]Search for more papers by this authorNathalie Ebran PhD
Department of Oncopharmacology, Antoine Lacassagne Comprehensive Cancer Centre, Nice cedex, France
Search for more papers by this authorNina Radosevic–Robin MD
Department of Pathology, Jean Perrin Comprehensive Cancer Centre, Clermont–Ferrand, France
ERTICa Research Group, University of Auvergne, Clermont–Ferrand, France
Search for more papers by this authorEmmanuel Chamorey PharmD
Department of Clinical Research, Innovation and Statistics (DRIS), Antoine Lacassagne Comprehensive Cancer Centre, Nice cedex, France
Search for more papers by this authorHedi Ben Yahia MSc
Department of Oncopharmacology, Antoine Lacassagne Comprehensive Cancer Centre, Nice cedex, France
Search for more papers by this authorSerge Marcie PhD
Department of Physics, Antoine Lacassagne Comprehensive Cancer Centre, Nice cedex, France
Search for more papers by this authorMathieu Gautier PhD
Department of Physics, Antoine Lacassagne Comprehensive Cancer Centre, Nice cedex, France
Search for more papers by this authorFrédérique Penault–Llorca MD, PhD
Department of Pathology, Jean Perrin Comprehensive Cancer Centre, Clermont–Ferrand, France
ERTICa Research Group, University of Auvergne, Clermont–Ferrand, France
Search for more papers by this authorGérard Milano PhD
Department of Oncopharmacology, Antoine Lacassagne Comprehensive Cancer Centre, Nice cedex, France
Search for more papers by this authorCorresponding Author
Alexandre Bozec MD, PhD
University Institute of the Face and Neck, Nice cedex, France
Corresponding author: A. Bozec, University Institute of the Face and Neck, 31 avenue de Valombrose, 06103 Nice, France. E-mail: [email protected]Search for more papers by this authorNathalie Ebran PhD
Department of Oncopharmacology, Antoine Lacassagne Comprehensive Cancer Centre, Nice cedex, France
Search for more papers by this authorNina Radosevic–Robin MD
Department of Pathology, Jean Perrin Comprehensive Cancer Centre, Clermont–Ferrand, France
ERTICa Research Group, University of Auvergne, Clermont–Ferrand, France
Search for more papers by this authorEmmanuel Chamorey PharmD
Department of Clinical Research, Innovation and Statistics (DRIS), Antoine Lacassagne Comprehensive Cancer Centre, Nice cedex, France
Search for more papers by this authorHedi Ben Yahia MSc
Department of Oncopharmacology, Antoine Lacassagne Comprehensive Cancer Centre, Nice cedex, France
Search for more papers by this authorSerge Marcie PhD
Department of Physics, Antoine Lacassagne Comprehensive Cancer Centre, Nice cedex, France
Search for more papers by this authorMathieu Gautier PhD
Department of Physics, Antoine Lacassagne Comprehensive Cancer Centre, Nice cedex, France
Search for more papers by this authorFrédérique Penault–Llorca MD, PhD
Department of Pathology, Jean Perrin Comprehensive Cancer Centre, Clermont–Ferrand, France
ERTICa Research Group, University of Auvergne, Clermont–Ferrand, France
Search for more papers by this authorGérard Milano PhD
Department of Oncopharmacology, Antoine Lacassagne Comprehensive Cancer Centre, Nice cedex, France
Search for more papers by this authorAbstract
Background
The purpose of this study was to investigate the effects of combining the phosphotidylinositol-3-kinase (PI3K) inhibitor buparlisib (BKM)120 with the anti-epidermal growth factor receptor (EGFR) agent cetuximab and radiotherapy (RT) on an orthotopic model of head and neck squamous cell carcinoma (HNSCC).
Methods
We evaluated the antitumor efficacy of BKM120, cetuximab, and RT, administered alone or in combination, using the human PIK3CA-mutated HNSCC cell line, CAL33, injected into the floor of the mouth of nude mice.
Results
Compared with control, the BKM120-cetuximab and the BKM120-cetuximab-RT combinations led to the highest tumor inhibition (p < .001). The highest inhibitory effect of treatments on cell proliferation, mitogen-activated protein kinase (MAPK) and PI3K/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathways were found with the BKM120-cetuximab association. The association of BKM120 and cetuximab with RT inhibited RT-induced activation of the MAPK pathway.
Conclusion
These results can serve as a preclinical rationale for innovative treatments combining PI3K inhibition with anti-EGFR therapies and irradiation in patients with HNSCC. © 2016 Wiley Periodicals, Inc. Head Neck 39: 151–159, 2017
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