Selective killing of ATM-or p53-deficient cancer cells through inhibition of ATR

PM Reaper, MR Griffiths, JM Long, JD Charrier… - Nature chemical …, 2011 - nature.com
PM Reaper, MR Griffiths, JM Long, JD Charrier, S MacCormick, PA Charlton, JMC Golec…
Nature chemical biology, 2011nature.com
Here we report a comprehensive biological characterization of a potent and selective small-
molecule inhibitor of the DNA damage response (DDR) kinase ATR. We show a profound
synthetic lethal interaction between ATR and the ATM-p53 tumor suppressor pathway in
cells treated with DNA-damaging agents and establish ATR inhibition as a way to transform
the outcome for patients with cancer treated with ionizing radiation or genotoxic drugs.
Abstract
Here we report a comprehensive biological characterization of a potent and selective small-molecule inhibitor of the DNA damage response (DDR) kinase ATR. We show a profound synthetic lethal interaction between ATR and the ATM-p53 tumor suppressor pathway in cells treated with DNA-damaging agents and establish ATR inhibition as a way to transform the outcome for patients with cancer treated with ionizing radiation or genotoxic drugs.
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