title: Sorafenib sensitizes head and neck squamous cell carcinoma cells to ionizing radiation.
abstract: OBJECTIVE
  There is a great need to improve the outcome of locoregionally advanced squamous cell carcinomas of the head and neck (HNSCC). Standard treatment includes a combination of surgery, radio- and chemotherapy. The addition of molecular targeting agents to conventional treatment may improve outcomes. In this study the Raf inhibitor sorafenib was used to increase the radiosensitivity of HNSCC cell lines.
  
  
  METHODS
  In a panel of six cell lines (A549, FaDu, UTSCC 60A, UTSCC 42A, UTSCC 42B, UTSCC 29) radiosensitivity was measured by colony formation assay and apoptosis and cell cycle analysis were performed by flow cytometry. DNA repair was analyzed by 53BP1 immunohistochemistry.
  
  
  RESULTS
  Sorafenib added prior to irradiation resulted in an increased cellular radiosensitivity (DEF0.5=1.11-1.84). Radiosensitization was not caused by an enhanced rate of apoptosis or cell cycle effects. In contrast, sorafenib was shown for the first time to block the repair of DNA double-strand breaks (DSB).
  
  
  CONCLUSIONS
  Our data suggest that sorafenib may be used to overcome the radioresistance of HNSCC through the inhibition of DSB repair.
authors: Department of Otorhinolaryngology and Head and Neck Surgery, University Medical Center Hamburg Eppendorf, Germany; Laboratory of Radiobiology & Experimental Radiooncology, University Medical Center Hamburg Eppendorf, Germany. Electronic address: simon.laban@uniklinik-ulm.de.
authors: Simon
authors: S
authors: Laban
authors: Leonhard
authors: L
authors: Steinmeister
authors: Lisa
authors: L
authors: Gleißner
authors: Tobias J
authors: TJ
authors: Grob
authors: Reidar
authors: R
authors: Grénman
authors: Cordula
authors: C
authors: Petersen
authors: Andreas
authors: A
authors: Gal
authors: Rainald
authors: R
authors: Knecht
authors: Ekkehard
authors: E
authors: Dikomey
authors: Malte
authors: M
authors: Kriegs
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D004260:DNA Repair; D006258:Head and Neck Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use*; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D000077157:Sorafenib; D000077195:Squamous Cell Carcinoma of Head and Neck; D048490:raf Kinases / Q000037:antagonists & inhibitors*
chemical_list: D010671:Phenylurea Compounds; D011838:Radiation-Sensitizing Agents; D009536:Niacinamide; D000077157:Sorafenib; D048490:raf Kinases
keywords: Head and neck squamous cell carcinoma; Irradiation; MAPK; Radiosensitization; Sorafenib