The drugs are expected to stop the cell cycle in G1 and prevent it from proceeding into S phase. CDK 4 and CDK 6 would be unable to phosphorylate RB, meaning transcription factor E2F would be inhibited and the proteins from genes that activate S phase would not be transcribed.
The cell would be stuck in cell cycle arrest, because the DNA is damaged, and the cell is not able to recover. If the cell is healthy and functioning normally, the hope is that it can get out of the arrest and reactivate the cell cycle.
Either the cell would stay in the arrested state (senescence) or the lack of growth signals would eventually cause the cellular stress response to activate the intrinsic apoptotic pathway. In the former scenario, the cell would remain alive as long as nutrients were present. In the latter case, the cell would shrink, collapse, and its contents would be absorbed and processed by neighbouring cells (qqb).…show more content… If the cells mostly remained in a senescent state, the tumour would not grow, and patient symptoms would not worsen. Ideally, the noncancerous cells affected by the CDK4/6 inhibitors would recover from the temporary G1 arrest and proceed through the cell cycle normally.
There are many reasons that this drug would not work, one being a mutation to RB that makes it consistently phosphorylated or otherwise unable to bind to E2F. The proteins that activate S phase would be constantly produced regardless of CDK4/6 activity, meaning repressing the CDKs would not have any
