1. Figure 3 The cell cycle and the role of CDK4/6 inhibition
Figure 3 | The cell cycle and the role of CDK4/6 inhibition. a | G1 arrest caused by cyclin-dependent kinase (CDK) 4/6 inhibition. CDK4/6 inhibitors bind to the ATP-binding domain of CDK4/6, thus competitively inhibiting the kinase activity of these proteins. The cyclin D–CDK4–retinoblastoma protein (RB1)–CDKN2A axis is commonly disrupted in cancer, for example, owing to overexpression of cyclin D or underexpression of CDKN2A. Under such conditions, and in the absence of an escape mechanism, CDK4/6 inhibitors can block the disinhibited phosphorylation of RB1, resulting in G1 arrest. b | Potential mechanisms of resistance to CDK4/6 inhibition. In cancer cells that lack RB1 function, the E2F transcription factor family members are constitutively active and CDK4/6 signalling is redundant. In RB1-replete cells, overexpression of cyclin E or loss of the inhibitor 1/kinase inhibitory protein (CIP/KIP) proteins might bypass CDK4/6 inhibition by activating CDK2. E2F amplification is posited as another mechanism for bypassing RB1. CKI; cyclin-dependent kinase inhibitor.
Turner, N. C. et al. (2016) Treating cancer with selective CDK4/6 inhibitors Nat. Rev. Clin. Oncol. doi: /nrclinonc