title: Combination of phosphotidylinositol-3-kinase targeting with cetuximab and irradiation: A preclinical study on an orthotopic xenograft model of head and neck cancer.
abstract: 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).
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors: University Institute of the Face and Neck, Nice cedex, France.
authors: Alexandre
authors: A
authors: Bozec
authors: Department of Oncopharmacology, Antoine Lacassagne Comprehensive Cancer Centre, Nice cedex, France.
authors: Nathalie
authors: N
authors: Ebran
authors: Department of Pathology, Jean Perrin Comprehensive Cancer Centre, Clermont-Ferrand, France.|ERTICa Research Group, University of Auvergne, Clermont-Ferrand, France.
authors: Nina
authors: N
authors: Radosevic-Robin
authors: Department of Clinical Research, Innovation and Statistics (DRIS), Antoine Lacassagne Comprehensive Cancer Centre, Nice cedex, France.
authors: Emmanuel
authors: E
authors: Chamorey
authors: Department of Oncopharmacology, Antoine Lacassagne Comprehensive Cancer Centre, Nice cedex, France.
authors: Hedi Ben
authors: HB
authors: Yahia
authors: Department of Physics, Antoine Lacassagne Comprehensive Cancer Centre, Nice cedex, France.
authors: Serge
authors: S
authors: Marcie
authors: Department of Physics, Antoine Lacassagne Comprehensive Cancer Centre, Nice cedex, France.
authors: Mathieu
authors: M
authors: Gautier
authors: Department of Pathology, Jean Perrin Comprehensive Cancer Centre, Clermont-Ferrand, France.|ERTICa Research Group, University of Auvergne, Clermont-Ferrand, France.
authors: Frédérique
authors: F
authors: Penault-Llorca
authors: Department of Oncopharmacology, Antoine Lacassagne Comprehensive Cancer Centre, Nice cedex, France.
authors: Gérard
authors: G
authors: Milano
mesh_terms: D000631:Aminopyridines / Q000627:therapeutic use*; D000818:Animals; D000074322:Antineoplastic Agents, Immunological / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D000068818:Cetuximab / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D051379:Mice; D008819:Mice, Nude; D009025:Morpholines / Q000627:therapeutic use*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D000077195:Squamous Cell Carcinoma of Head and Neck; D023041:Xenograft Model Antitumor Assays
chemical_list: D000631:Aminopyridines; D000074322:Antineoplastic Agents, Immunological; D009025:Morpholines; C571178:NVP-BKM120; D000081082:Phosphoinositide-3 Kinase Inhibitors; D000068818:Cetuximab
keywords: epidermal growth factor receptor (EGFR); head and neck cancer; phosphatidylinositol 3-kinase (PIK3CA); radiotherapy; targeted therapy