Kevin B Elmore1, Lauren R Schaff2. 1. Department of Neurology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA. 2. Department of Neurology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA. schaffl@mskcc.org.
Abstract
PURPOSE OF REVIEW: This review discusses current and investigative strategies for targeting DNA repair in the management of glioma. RECENT FINDINGS: Recent strategies in glioma treatment rely on the production of overwhelming DNA damage and inhibition of repair mechanisms, resulting in lethal cytotoxicity. Many strategies are effective in preclinical glioma models while clinical feasibility remains under investigation. The presence of glioma biomarkers, including IDH mutation and/or MGMT promoter methylation, may confer particular susceptibility to DNA damage and inhibition of repair. These biomarkers have been adopted as eligibility criteria in the design of multiple ongoing clinical trials. Targeting DNA repair mechanisms with novel agents or therapeutic combinations is a promising approach to the treatment of glioma. Further investigations are underway to optimize this approach in the clinical setting.
PURPOSE OF REVIEW: This review discusses current and investigative strategies for targeting DNA repair in the management of glioma. RECENT FINDINGS: Recent strategies in glioma treatment rely on the production of overwhelming DNA damage and inhibition of repair mechanisms, resulting in lethal cytotoxicity. Many strategies are effective in preclinical glioma models while clinical feasibility remains under investigation. The presence of glioma biomarkers, including IDH mutation and/or MGMT promoter methylation, may confer particular susceptibility to DNA damage and inhibition of repair. These biomarkers have been adopted as eligibility criteria in the design of multiple ongoing clinical trials. Targeting DNA repair mechanisms with novel agents or therapeutic combinations is a promising approach to the treatment of glioma. Further investigations are underway to optimize this approach in the clinical setting.
Entities:
Keywords:
ATM inhibitor; DNA damage response; DNA repair; Glioblastoma; Glioma; PARP inhibitor
Authors: Ian Hickson; Yan Zhao; Caroline J Richardson; Sharon J Green; Niall M B Martin; Alisdair I Orr; Philip M Reaper; Stephen P Jackson; Nicola J Curtin; Graeme C M Smith Journal: Cancer Res Date: 2004-12-15 Impact factor: 12.701
Authors: Laura Biddlestone-Thorpe; Muhammad Sajjad; Elizabeth Rosenberg; Jason M Beckta; Nicholas C K Valerie; Mary Tokarz; Bret R Adams; Alison F Wagner; Ashraf Khalil; Donna Gilfor; Sarah E Golding; Sumitra Deb; David G Temesi; Alan Lau; Mark J O'Connor; Kevin S Choe; Luis F Parada; Sang Kyun Lim; Nitai D Mukhopadhyay; Kristoffer Valerie Journal: Clin Cancer Res Date: 2013-04-25 Impact factor: 12.531
Authors: Christopher B Jackson; Seth I Noorbakhsh; Ranjini K Sundaram; Aravind N Kalathil; Sachita Ganesa; Lanqi Jia; Hank Breslin; Danielle M Burgenske; Oren Gilad; Jann N Sarkaria; Ranjit S Bindra Journal: Cancer Res Date: 2019-07-04 Impact factor: 12.701
Authors: Frank T Zenke; Astrid Zimmermann; Christian Sirrenberg; Heike Dahmen; Vladimir Kirkin; Ulrich Pehl; Thomas Grombacher; Claudia Wilm; Thomas Fuchss; Christiane Amendt; Lyubomir T Vassilev; Andree Blaukat Journal: Mol Cancer Ther Date: 2020-03-27 Impact factor: 6.261
Authors: E Fokas; R Prevo; J R Pollard; P M Reaper; P A Charlton; B Cornelissen; K A Vallis; E M Hammond; M M Olcina; W Gillies McKenna; R J Muschel; T B Brunner Journal: Cell Death Dis Date: 2012-12-06 Impact factor: 8.469
Authors: Stephen T Durant; Li Zheng; Yingchun Wang; Kan Chen; Lingli Zhang; Tianwei Zhang; Zhenfan Yang; Lucy Riches; Antonio G Trinidad; Jacqueline H L Fok; Tom Hunt; Kurt G Pike; Joanne Wilson; Aaron Smith; Nicola Colclough; Venkatesh Pilla Reddy; Andrew Sykes; Annika Janefeldt; Peter Johnström; Katarina Varnäs; Akihiro Takano; Stephanie Ling; Jonathan Orme; Jonathan Stott; Caroline Roberts; Ian Barrett; Gemma Jones; Martine Roudier; Andrew Pierce; Jasmine Allen; Jenna Kahn; Amrita Sule; Jeremy Karlin; Anna Cronin; Melissa Chapman; Kristoffer Valerie; Ruth Illingworth; Martin Pass Journal: Sci Adv Date: 2018-06-20 Impact factor: 14.136
Authors: Shafiq U Ahmed; Ross Carruthers; Lesley Gilmour; Salih Yildirim; Colin Watts; Anthony J Chalmers Journal: Cancer Res Date: 2015-08-17 Impact factor: 12.701