Notable exceptions were two RB1-mutated lines, the osteosarcoma line SAOS2 and the cervical cancer cell line C-33A, where combination treatment had additive or less than additive effects (Fig. 4b, c), consistent with the notion that RB1 is a critical downstream effector of CDK4/6 and that RB1 loss renders cells unresponsive to CDK4/6is. The gene discussed is RB1; the disease is osteosarcoma.