Selective DNA-Pkcs Inhibition Extends the Therapeutic Index of Localized Radiotherapy and Chemotherapy
Selective DNA-PKcs inhibition extends the therapeutic index of localized radiotherapy and chemotherapy Catherine E. Willoughby, … , Anderson J. Ryan, Stephen R. Wedge J Clin Invest. 2019. https://doi.org/10.1172/JCI127483. Research Article Oncology Therapeutics Graphical abstract Find the latest version: https://jci.me/127483/pdf The Journal of Clinical Investigation RESEARCH ARTICLE Selective DNA-PKcs inhibition extends the therapeutic index of localized radiotherapy and chemotherapy Catherine E. Willoughby,1 Yanyan Jiang,2 Huw D. Thomas,1 Elaine Willmore,1 Suzanne Kyle,1 Anita Wittner,1 Nicole Phillips,1 Yan Zhao,1 Susan J. Tudhope,1 Lisa Prendergast,1 Gesa Junge,1 Luiza Madia Lourenco,2 M. Raymond V. Finlay,3 Paul Turner,3 Joanne M. Munck,4 Roger J. Griffin,5 Tommy Rennison,5 James Pickles,5 Celine Cano,5 David R. Newell,1 Helen L. Reeves,1,6 Anderson J. Ryan,2 and Stephen R. Wedge1 1Cancer Research UK Newcastle Drug Discovery Unit, Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom. 2Cancer Research UK and UK Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, United Kingdom. 3Medicinal Chemistry, Oncology, IMED Biotech Unit, AstraZeneca, Cambridge, United Kingdom. 4Astex Pharmaceuticals, Cambridge, United Kingdom. 5Cancer Research UK Newcastle Drug Discovery Unit, Chemistry, School of Natural and Environmental Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom. 6Hepatopancreatobiliary Multidisciplinary Team, Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom. Potentiating radiotherapy and chemotherapy by inhibiting DNA damage repair is proposed as a therapeutic strategy to improve outcomes for patients with solid tumors.
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