Figure 2.

Increasing reliance on the G2/M checkpoint allows cells to bypass the G1/M deficiencies caused by CDK4/6 inhibitors. Wee1 works at the G2/M checkpoint to stall mitosis and induce DNA repair so that cells can progress in the presence of CDK inhibitors. MK1775 works here to inhibit the action of Wee1, thus preventing repair from occurring and so the cell cannot continue through division. Additionally, at G2/M, CDK7 phosphorylates CDK1 to cause cell cycle progression via cyclin B1. THZ1 is an agent that inhibits CDK7 to prevent this method of cell cycle progression.