Pre-clinical work demonstrates that cell lines with high levels of phosphorylated p27kip1 were resistant to CDK4/6 inhibitor, but co-administration of saracatinib restored CDK4/6 inhibitor sensitivity in vitro and in vivo (albeit in a colorectal cancer model).[25] There is an ongoing phase I study investigating the combination of another Src inhibitor (bosutinib) with a CDK4/6 inhibitor and fulvestrant in advanced breast cancer refractory to a CDK4/6 inhibitor (NCT03854903). Here, CDK4 is linked to breast carcinoma.