Cell cycle control
The cell cycle involves regulated cell growth, replication, and division. The cell cycle includes four distinct phases: G1 (gap phase 1), S (DNA synthesis), G2 (gap phase 2), and M (mitosis). Cell cycle regulation (both activation and inhibition) is dependent upon specific cell cycle checkpoints, which prevent abnormal cell cycle activation and continuation. For example, the G2/M checkpoint ensures that cells containing damaged DNA do not enter mitosis. These cell cycle checkpoints are controlled by the coordinated action of CDK+cyclin binding pairs including CDK4/6+cyclin D, RB1/E2F, CDK2+cyclin E, CDK2+cyclin A, CDK1+cyclin A, CDK1+cyclin B. 
Figure 1. The cell cycle is a set of processes through which a cell divides to become two identical daughter cells. The cell cycle encompasses four phases including G1 (gap phase 1), S (DNA synthesis), G2 (gap phase 2), and M (mitosis). The cell cycle is controlled by the complex interplay of cyclin-dependent kinases (CDK -1, -2, -4, -6, -8, -12) and cyclins (cyclin -A, -B, -D, -E). Heterodimers of cyclins and CDKs function at different points in the cycle. There are several checks and balances, called checkpoints, in the cell cycle to ensure integrity of daughter cells. Checkpoints include the G1/S checkpoint and the G2/M checkpoint. Of particular relevance, p21 and p27 function as regulators of the G1 and S checkpoints. These checkpoints become important in the setting of DNA damage. DNA damage activates these checkpoints to ensure genomic integrity by repairing damaged DNA or forcing the cell to enter a programmed cell death pathway if DNA cannot be repaired. Checkpoints and DNA damage responses are altered in numerous malignancies. Specific nodes in the pathway that are therapeutically actionable are noted.
TP53, CCND1, and CDK4 are the most frequent biomarkers that serve as inclusion criteria in therapies targeting the cell cycle control pathway.
Biomarkers in the cell cycle control pathway serve as inclusion eligibility criteria in 217 clinical trials, of which 188 are open and 29 are closed. The genes TP53, CHEK2, CHEK1, CDKN2A, and CDK12 on this pathway most frequently harbor alterations that are inclusion eligibility criteria for clinical trials.
Of the trials that contain alteration(s) in the cell cycle control pathway as inclusion criteria, 3 are early phase 1 (3 open), 3 are n/a (3 open), 45 are phase 1 (32 open), 31 are phase 1/phase 2 (28 open), 122 are phase 2 (111 open), 4 are phase 2/phase 3 (4 open), 8 are phase 3 (6 open), and 1 is phase 4 (1 open) .