Furthermore, Ewing sarcoma cells are particularly sensitive to further exacerbation of DNA replication stress through inhibition of ribonucleotide reductase (RNR), which is the rate-limiting enzyme in the synthesis of dNTPs, and blockade of the replication stress response using ATR, checkpoint kinase 1 (CHK1), and WEE1 inhibitors (3, 17–29). Here, NR2E3 is linked to Ewing sarcoma.