dc.contributor.author | Bhide, SA | |
dc.contributor.author | Thway, K | |
dc.contributor.author | Lee, J | |
dc.contributor.author | Wong, K | |
dc.contributor.author | Clarke, P | |
dc.contributor.author | Newbold, KL | |
dc.contributor.author | Nutting, CM | |
dc.contributor.author | Harrington, KJ | |
dc.date.accessioned | 2017-03-01T12:09:43Z | |
dc.date.issued | 2016-09-27 | |
dc.identifier.citation | British journal of cancer, 2016, 115 (7), pp. 825 - 830 | |
dc.identifier.issn | 0007-0920 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/435 | |
dc.identifier.eissn | 1532-1827 | |
dc.identifier.doi | 10.1038/bjc.2016.266 | |
dc.description.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. | |
dc.format | Print-Electronic | |
dc.format.extent | 825 - 830 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | NATURE PUBLISHING GROUP | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-sa/4.0 | |
dc.subject | Humans | |
dc.subject | Papillomaviridae | |
dc.subject | Papillomavirus Infections | |
dc.subject | Carcinoma, Squamous Cell | |
dc.subject | Oropharyngeal Neoplasms | |
dc.subject | Organoplatinum Compounds | |
dc.subject | Neoplasm Proteins | |
dc.subject | DNA, Neoplasm | |
dc.subject | Antineoplastic Agents, Alkylating | |
dc.subject | Antineoplastic Combined Chemotherapy Protocols | |
dc.subject | Treatment Outcome | |
dc.subject | Pilot Projects | |
dc.subject | S Phase | |
dc.subject | DNA Repair | |
dc.subject | Rad51 Recombinase | |
dc.subject | DNA Breaks, Double-Stranded | |
dc.subject | Chemoradiotherapy | |
dc.title | Delayed DNA double-strand break repair following platin-based chemotherapy predicts treatment response in head and neck squamous cell carcinoma. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2016-08-01 | |
rioxxterms.versionofrecord | 10.1038/bjc.2016.266 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by-nc-sa/4.0 | |
rioxxterms.licenseref.startdate | 2016-09 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | British journal of cancer | |
pubs.issue | 7 | |
pubs.notes | 12 months | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology/Targeted Therapy | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Targeted Therapy | |
pubs.organisational-group | /ICR/Primary Group/Royal Marsden Clinical Units | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology/Targeted Therapy | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Targeted Therapy | |
pubs.organisational-group | /ICR/Primary Group/Royal Marsden Clinical Units | |
pubs.publication-status | Published | |
pubs.volume | 115 | |
pubs.embargo.terms | 12 months | |
icr.researchteam | Targeted Therapy | |
dc.contributor.icrauthor | Harrington, Kevin | |