De Angelis et al.44 revealed an intriguing connection between resistance to CDK4/6 inhibitors and abnormal activation of IFN-signaling, as showcased in both HR+/HER2− breast cancer cell lines of the Luminal B phenotype45, as well as patient tumors from the NeoPalAna and neoMONARCH neoadjuvant clinical trials. The gene discussed is CDK4; the disease is breast carcinoma.