In breast cancer, IRDS genes, including Isg15, Stat1, Mx1, Oas1, Ifit1, Ifit3, and Ifi44, are associated with resistance to therapies, and their downregulation resensitizes triple-negative breast cancer (TNBC) cells to chemo- and radiotherapy113, suggesting that targeting IRDS genes in cancer could be a promising approach to increase therapeutic efficacy. Here, ISG15 is linked to triple-negative breast carcinoma.