DNA double strand break repair defect and sensitivity to poly ADP-ribose polymerase (PARP) inhibition in human papillomavirus 16-positive head and neck squamous cell carcinoma

Oncotarget
Alice N WeaverEddy S Yang

Abstract

Patients with human papillomavirus-positive (HPV+) head and neck squamous cell carcinomas (HNSCCs) have increased response to radio- and chemotherapy and improved overall survival, possibly due to an impaired DNA damage response. Here, we investigated the correlation between HPV status and repair of DNA damage in HNSCC cell lines. We also assessed in vitro and in vivo sensitivity to the PARP inhibitor veliparib (ABT-888) in HNSCC cell lines and an HPV+ patient xenograft. Repair of DNA double strand breaks (DSBs) was significantly delayed in HPV+ compared to HPV- HNSCCs, resulting in persistence of γH2AX foci. Although DNA repair activators 53BP1 and BRCA1 were functional in all HNSCCs, HPV+ cells showed downstream defects in both non-homologous end joining and homologous recombination repair. Specifically, HPV+ cells were deficient in protein recruitment and protein expression of DNA-Pk and BRCA2, key factors for non-homologous end joining and homologous recombination respectively. Importantly, the apparent DNA repair defect in HPV+ HNSCCs was associated with increased sensitivity to the PARP inhibitor veliparib, resulting in decreased cell survival in vitro and a 10-14 day tumor growth delay in vivo. These results support the ...Continue Reading

References

May 4, 2000·Journal of the National Cancer Institute·M L GillisonD Sidransky
Apr 8, 2003·Proceedings of the National Academy of Sciences of the United States of America·Kai Rothkamm, Markus Löbrich
Sep 6, 2003·International Journal of Radiation Oncology, Biology, Physics·Floris M WachtersHarm H Kampinga
Jan 13, 2006·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Paul M WeinbergerAmanda Psyrri
Feb 10, 2006·The New England Journal of Medicine·James A BonnerK Kian Ang
Apr 5, 2007·Nature Protocols·Peggy L Olive, Judit P Banáth
Feb 19, 2008·Nature Biotechnology·Gary K GeissKrassen Dimitrov
Mar 11, 2009·Molecular and Cellular Biology·Michalis FragkosPeter Beard
Feb 6, 2010·Proceedings of the National Academy of Sciences of the United States of America·Cristian BoboilaFrederick W Alt
Feb 6, 2010·Proceedings of the National Academy of Sciences of the United States of America·Denise Campisi HeganPeter M Glazer
Jun 10, 2010·The New England Journal of Medicine·K Kian AngMaura L Gillison
Jun 17, 2010·Cancer Research·Ponnari GottipatiThomas Helleday
Feb 26, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Benjamin J MoellerDavid L Schwartz
Apr 8, 2011·Current Protocols in Molecular Biology·Meghana M Kulkarni
May 10, 2011·BMC Biotechnology·Patricia P ReisSuzanne Kamel-Reid
Nov 25, 2011·Molecular Cancer Research : MCR·Lisa A TobinFeyruz V Rassool
May 9, 2012·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Maura L GillisonK Kian Ang
Feb 13, 2013·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Moritz BirkelbachHenning Willers
Apr 23, 2013·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·Thorsten RieckmannMalte Kriegs
Nov 19, 2013·Pharmaceutical Patent Analyst·Monica Wielgos, Eddy S Yang
Mar 7, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Andrew SewellWendell G Yarbrough
Sep 14, 2014·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·Jung Wook ParkRandall J Kimple
Oct 1, 2014·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Christine H ChungQuynh-Thu Le
Dec 4, 2014·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·Julian David GüsterThorsten Rieckmann

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Citations

Aug 29, 2018·The Laryngoscope·Shayan CheraghlouBenjamin L Judson
May 17, 2019·Cancers of the Head & Neck·Cassie PanWendell G Yarbrough
Dec 19, 2019·Frontiers in Immunology·Mine Özcan-WahlbrinkAngelika B Riemer
Mar 5, 2016·Current Treatment Options in Oncology·Fong W Liu, Krishnansu S Tewari
Apr 30, 2016·Oncotarget·Chia-Jung BuschThorsten Rieckmann
Oct 9, 2019·Proceedings of the National Academy of Sciences of the United States of America·Jonathan E LeemanDaniel S Higginson
Sep 26, 2019·Frontiers in Oncology·Qi LiuMary Helen Barcellos-Hoff
Jul 3, 2020·Expert Reviews in Molecular Medicine·Chumin Zhou, Jason L Parsons
May 23, 2018·Journal of Experimental & Clinical Cancer Research : CR·Hye Jeong ParkKyu Yun Jang
Jul 10, 2019·International Journal of Cancer. Journal International Du Cancer·Rüveyda DokSandra Nuyts
Aug 9, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Qi LiuMary Helen Barcellos-Hoff
Dec 30, 2016·Molecular Cancer Research : MCR·Monica E WielgosEddy S Yang
Jun 22, 2017·Annals of Oncology : Official Journal of the European Society for Medical Oncology·M TabernaR Mesía
Jul 2, 2021·Molecular Imaging·Navjot GuruThomas Reiner
Aug 28, 2021·Biomedicines·Morena FasanoRaffaele Solla
Aug 31, 2021·Seminars in Radiation Oncology·Pippa F CosperRandall J Kimple

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Methods Mentioned

BETA
xenograft
electrophoresis
transfection
flow cytometry
xenografts
transfections
Assay

Software Mentioned

NanoString nSolver
GraphPad
GraphPad Prism

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