Figure 1.

Cell cycle‐specific mechanisms for the resistance to CDK4/6 inhibitors. Multiple factors involved in the regulation of cell cycle are associated with resistance to CDK4/6 inhibitors. Loss of drug target genes, such as RB and FZR1, as well as overexpression of various genes which are directly or indirectly involved in the progression of cell cycle, as shown in Figure 1, are responsible for resistance to CDK4/6 inhibitors. Abbreviations: CDK, Cyclin dependent kinase; RB, Retinoblastoma protein; CHK1, Checkpoint kinase 1; STAT3, Signal transducer and activator of transcription 3; VEGF‐A, Vascular endothelial growth factor A; HDAC, Histone deacetylases; MDM2, Mouse double minute 2 homolog. [Color figure can be viewed at wileyonlinelibrary.com]