We and others have identified that Ewing sarcoma tumors are sensitive to inhibitors of RNR and that inhibition of the ATR-CHK1 pathway, which plays a key role in orchestrating the cellular response to DNA replication stress, sensitizes Ewing sarcoma cells to RNR inhibitors (20–22, 36, 67). The gene discussed is NR2E3; the disease is Ewing sarcoma.