To this end, we generated cell line models of therapy-resistant luminal breast cancer by culturing MCF7 (p53 wild-type) and T47D (p53-mutant) cells in increasing concentrations of the CDK4/6i abemaciclib, the selective estrogen receptor degrader fulvestrant, or their combination until resistance was observed (defined as sustained growth in 500 nmol/L of abemaciclib, 100 nmol/L of fulvestrant, or 500 nmol/L/100 nmol/L, respectively, for the combination; Supplementary Fig. S6A). Here, TP53 is linked to breast carcinoma.