Delayed DNA double-strand break repair following platin-based chemotherapy predicts treatment response in head and neck squamous cell carcinoma.
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Embargo End Date
ICR Authors
Authors
Bhide, SA
Thway, K
Lee, J
Wong, K
Clarke, P
Newbold, KL
Nutting, CM
Harrington, KJ
Thway, K
Lee, J
Wong, K
Clarke, P
Newbold, KL
Nutting, CM
Harrington, KJ
Document Type
Journal Article
Date
2016-09-27
Date Accepted
2016-08-01
Abstract
INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Citation
British journal of cancer, 2016, 115 (7), pp. 825 - 830
Source Title
Publisher
NATURE PUBLISHING GROUP
ISSN
0007-0920
eISSN
1532-1827
Research Team
Targeted Therapy