The investigators demonstrated that, in breast cancer cells, the ablation of PTEN through increased AKT activation was sufficient to promote resistance to CDK4/6 inhibition (ribociclib and letrozole) in vitro and in vivo; PTEN loss resulted in the exclusion of p27 from the nucleus, leading to increased activation of both CDK4 and CDK2 [49]. The gene discussed is CDK4; the disease is breast cancer.