Figure 1.

Activating and deactivating mutations identified to date that allow cells to survive in the presence of CDK4/6 inhibitors. Activation of cyclin D1, CDK4/6, CDK2, cyclin E1, E2F, PDK1, mTOR, CDK7, Wee1, PDLIM7, MDM2, FGFR1, KRAS, the lysosome, and the autophagosome can help cells push through the cell cycle when CDK4/6 are pharmacologically inhibited. Deactivation of RB, FAT1, and CDH18 can lead to similar effects on cell cycle progression and overall cell survival. Mutations in each of these proteins and cellular components help the cell to survive via a variety of mechanisms, which are detailed in Section 5.