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Lookup NU author(s): Dr Tao Chen, Dr Peter Stephens, Fiona Middleton, Professor Nicola CurtinORCiD
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Cell survival following DNA damage depends on activating checkpoints to arrest proliferation. Most cancer cells have dysregulated G1 checkpoints making them dependent on their S and G2 checkpoints, which are activated by ATR/Chk1 signalling. Thus, inhibiting ATR or Chk1 should selectively sensitise cancer cells to DNA damage. Genetic inactivation of ATR and Chk1 abrogates cell cycle arrest and enhances cytotoxicity following exposure to DNA-damaging agents. Similar effects were seen with small-molecule Chk1 inhibitors in preclinical studies, and clinical trial data are starting to emerge. Recently, potent ATR inhibitors have been identified that also sensitise cancer cells in vitro. ATR and Chk1 inhibitors might also cause 'synthetic lethality' in tumour cells defective in defined DNA repair pathways
Author(s): Chen T, Stephens PA, Middleton FK, Curtin NJ
Publication type: Article
Publication status: Published
Journal: Drug Discovery Today
Year: 2012
Volume: 17
Issue: 5-6
Pages: 194-202
Print publication date: 14/12/2011
ISSN (print): 1359-6446
ISSN (electronic): 1878-5832
Publisher: Elsevier Ltd
URL: http://dx.doi.org/10.1016/j.drudis.2011.12.009
DOI: 10.1016/j.drudis.2011.12.009
PubMed id: 22192883
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