title: Delayed DNA double-strand break repair following platin-based chemotherapy predicts treatment response in head and neck squamous cell carcinoma.
abstract: The aim of this study was to investigate if defective repair of DNA double-strand break (DSB) in head and neck squamous cell carcinoma (HNSCC) could be used as an early predictor of treatment response.
  
  
  
  Tumour biopsy 24-36 h following induction chemotherapy (IC) and pre-treatment biopsies were stained for RAD51 and geminin (S-phase marker) for immunofluorescence in patients with HNSCC. The difference between RAD51 score (percentage of geminin-positive cells that were also positive for RAD51) was calculated for the two specimens. Tumours with a percentage difference of⩽10% were deemed to have repaired IC-induced DSBs, and were classified as 'RAD51 negative'. Response at 3 months post treatment and human papilloma virus (HPV) status were assessed.
  
  
  
  Thirteen pairs of samples were available for analyses. Three samples were classified as RAD51 negative and 10 as RAD51 positive at 24 h post IC. All of the three patients with tumours classified as RAD51 negative had partial response or progressive disease and the 10 patients with tumours deemed RAD51 positive had a complete response. 100% of the HPV-positive tumours were RAD51 positive and had a complete response.
  
  
  
  We have demonstrated that impaired DSB DNA repair may underlie enhanced treatment sensitivity of HPV-positive HNSCC and repair capacity following platinum-induced DNA damage predicts response in HNSCC. This has potential as a biomarker for patient selection in trials of DNA damage response pathway modulation.
authors: Head and Neck unit, The Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK.|Downs Road, Sutton SM2 5PT, UK.|Radiotherapy and Imaging, The Institute of Cancer Research, 123 Old Brompton Road, London SW7 3RP, UK.
authors: S A
authors: SA
authors: Bhide
authors: Head and Neck unit, The Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK.|Downs Road, Sutton SM2 5PT, UK.
authors: K
authors: K
authors: Thway
authors: Radiotherapy and Imaging, The Institute of Cancer Research, 123 Old Brompton Road, London SW7 3RP, UK.
authors: J
authors: J
authors: Lee
authors: Head and Neck unit, The Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK.|Downs Road, Sutton SM2 5PT, UK.|Radiotherapy and Imaging, The Institute of Cancer Research, 123 Old Brompton Road, London SW7 3RP, UK.
authors: K
authors: K
authors: Wong
authors: Head and Neck unit, The Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK.|Downs Road, Sutton SM2 5PT, UK.
authors: P
authors: P
authors: Clarke
authors: Head and Neck unit, The Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK.|Downs Road, Sutton SM2 5PT, UK.|Radiotherapy and Imaging, The Institute of Cancer Research, 123 Old Brompton Road, London SW7 3RP, UK.
authors: K L
authors: KL
authors: Newbold
authors: Head and Neck unit, The Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK.|Downs Road, Sutton SM2 5PT, UK.|Radiotherapy and Imaging, The Institute of Cancer Research, 123 Old Brompton Road, London SW7 3RP, UK.
authors: C M
authors: CM
authors: Nutting
authors: Head and Neck unit, The Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK.|Downs Road, Sutton SM2 5PT, UK.|Radiotherapy and Imaging, The Institute of Cancer Research, 123 Old Brompton Road, London SW7 3RP, UK.
authors: K J
authors: KJ
authors: Harrington
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000628:therapy*; D059248:Chemoradiotherapy; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D004273:DNA, Neoplasm / Q000187:drug effects / Q000235:genetics; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000494:pharmacology; D009959:Oropharyngeal Neoplasms / Q000235:genetics / Q000628:therapy*; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000235:genetics / Q000628:therapy; D010865:Pilot Projects; D051135:Rad51 Recombinase / Q000235:genetics / Q000378:metabolism; D016196:S Phase / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D009944:Organoplatinum Compounds; C495153:RAD51 protein, human; D051135:Rad51 Recombinase