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

  • Nat Chem Biol. 2011 Apr 13;7(7):428-30. doi: 10.1038/nchembio.573.
Philip M Reaper  1 ,  Matthew R Griffiths ,  Joanna M Long ,  Jean-Damien Charrier ,  Somhairle Maccormick ,  Peter A Charlton ,  Julian M C Golec ,  John R Pollard
Affiliations
  • 1. Vertex Pharmaceuticals (Europe), Abingdon, Oxfordshire, UK.
PMID: 21490603 DOI: 10.1038/nchembio.573
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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