ATM and urinary bladder cancer: In ATM-deficient cells, olaparib has been shown to induce replication-dependent phosphorylation of histone H2AX,40,42,43 autophosphorylation of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) on serine 2056,44,45 phosphorylation of p53 on serine 15 and upregulation of p21.22 In bladder cancer cells, olaparib was shown to induce reactive oxygen species (ROS) and ROS production was potentiated in the absence of ATM,43 suggesting that olaparib can induce ROS-mediated cell death.