Inhibiting ribonucleotide reductase with hydroxyurea halts replication forks and causes DSBs.137 Hydroxyurea-induced DNA damage upregulates ISG expression in BRCA1-deficient breast cancer cells in a cGAS/STING-dependent manner.133 In addition, hydroxyurea treatment increased PD-L1 expression on cancer cells, suggesting that the combination of antimetabolite drugs and immune checkpoint inhibitors may show a synergistic effect. This evidence concerns the gene CD274 and cancer.