title: Effects of neratinib and combination with irradiation and chemotherapy in head and neck cancer cells.
abstract: OBJECTIVE
  Prognosis of patients with head and neck squamous cell carcinoma (HNSCC) is still poor. Novel therapeutic approaches are of great interest to improve the effects of radiochemotherapy. We evaluated the effects of tyrosine kinase inhibitor neratinib on HNSCC cell lines CAL27, SCC25 and FaDu as a single agent and in combination with irradiation and chemotherapy.
  
  
  METHODS
  Effects of neratinib were evaluated in HNSCC cell lines CAL27, SCC25 and FaDu. Effect on cell viability of neratinib and combination with cisplatin and irradiation was measured using CCK-8 assays and clonogenic assays. Western blot analysis was performed to distinguish the effect on epithelial growth factor receptor and HER2 expression. Apoptosis was evaluated by flow cytometry analysis.
  
  
  RESULTS
  Growth inhibition was achieved in all cell lines, whereas combination of cisplatin and neratinib showed greater inhibition than each agent alone. Apoptosis was induced in all cell lines. Combination of neratinib with irradiation or cisplatin showed significantly increased apoptosis. In clonogenic assays, significant growth inhibition was observed in all investigated cell lines.
  
  
  CONCLUSIONS
  Neratinib, as a single agent or in combination with chemo-irradiation, may be a promising treatment option for patients with head and neck cancer.
authors.affiliation: Department of Otorhinolaryngology - Head and Neck Surgery, Medical University of Vienna, Austria.
authors.forename: S
authors.initials: S
authors.lastname: Schneider
authors.affiliation: Department of Otorhinolaryngology - Head and Neck Surgery, Medical University of Graz, Austria.
authors.forename: D
authors.initials: D
authors.lastname: Thurnher
authors.affiliation: Department of Otorhinolaryngology - Head and Neck Surgery, Medical University of Vienna, Austria.
authors.forename: L
authors.initials: L
authors.lastname: Kadletz
authors.affiliation: Department of Cranio-, Maxillofacial and Oral Surgery, Medical University of Vienna, Austria.
authors.forename: R
authors.initials: R
authors.lastname: Seemann
authors.affiliation: Department of Otorhinolaryngology - Head and Neck Surgery, Medical University of Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Brunner
authors.affiliation: Department of Otorhinolaryngology - Head and Neck Surgery, Medical University of Vienna, Austria.
authors.forename: U
authors.initials: U
authors.lastname: Kotowski
authors.affiliation: Department of Radiotherapy, Medical University of Vienna, Austria.
authors.forename: R
authors.initials: R
authors.lastname: Schmid
authors.affiliation: Department of Otorhinolaryngology - Head and Neck Surgery, Medical University of Vienna, Austria.
authors.forename: C
authors.initials: C
authors.lastname: Lill
authors.affiliation: Department of Otorhinolaryngology - Head and Neck Surgery, Medical University of Vienna, Austria. gregor.heiduschka@meduniwien.ac.at.
authors.forename: G
authors.initials: G
authors.lastname: Heiduschka
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D005434:Flow Cytometry; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D006801:Humans; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011804:Quinolines / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D011804:Quinolines; D011505:Protein-Tyrosine Kinases; C487932:neratinib
keywords: HKI-272; chemotherapy; head and neck squamous cell carcinoma; irradiation; neratinib; tyrosine kinase inhibitor