Figure 1: Regulation of cell cycle. Cell cycle is divided into four distinct phases (G<sub>1</sub>, S, G2, and M). Each phase of the cell cycle is regulated by cyclins, cyclindependent kinases (CDKs), and cyclin-dependent kinase inhibitors (CDKIs). CDKs are the key regulators of cell cycle which are in turn positively and negatively regulated by cyclins and CDKIs, respectively. G0 represents exit from the cell cycle. The restriction point governs the transition point beyond which progression through the cell cycle is independent of external stimuli. The entry into the synthetic phase i.e. S phase is governed by Retinoblastoma gene product (Rb) . Hypophosphorylated Rb forms a complex with a group of transcription factors, E2F. When Rb is inactivated by CDK2-, CDK4, or CDK6-mediated phosphorylation, E2F transcription factors are released, resulting in progression into S phase and transcription of a range of targets involved in chemotherapy sensitivity.