CDK4 and breast cancer: Since the complete Rb pathway is essential for CDK4/6i, Rb pathway proteins has been proven to be as in vitro biomarkers.[3,16] For example, a recent study showed that complete G1/S transmission is a reliable prognostic marker for HR+/HER2− BC patients.[16] Finally, the study of Abemaciclib shows that the expression level of ER and Rb can influence the curative effect to Abemaciclib.[17] Another study found that tumors with RB1 mutations or deletions were highly sensitive to Aurora kinase inhibitors, suggesting the possibility of reversing CDK4/6i resistance.[18]