CDK4 and breast cancer: Past studies have demonstrated several mechanisms underlying the resistance of BC cells to CDK4/6 inhibitors, including loss of, or mutations in RB1, altered CDK4/6 and CDK2 signaling pathways, and activation of growth signaling pathways (McCartney et al. 2019; Portman et al. 2018; Schoninger and Blain 2020; Guarducci et al. 2018).