In this study, by performing a whole genome-wide CRISPR/Cas9 screen, we have unveiled a role for the coagulation factor IX (F9) as an important regulator of senescence induced by CDK4/6 inhibitors in ER+ breast cancer cell lines and other cancer cells, thus identifying genes whose loss can predicted a lack of response to Palbo. Here, CDK4 is linked to breast carcinoma.