1. Figure 4 Possible combination therapies CDK4/6 inhibitors
Figure 4 | Possible combination therapies CDK4/6 inhibitors. a | The cyclin-dependent kinases (CDKs) and cyclins act both in parallel with and downstream of cellular signal-transduction pathways and oestrogen-signalling pathways to promote cell-cycle progression. Activation of the MAPK and PI3K pathways by receptor tyrosine kinases (RTKs) promotes cell-cycle progression through upregulation of D-type and E-type cyclins. RTK signalling activates CDK4/6 signalling, but might also promote CDK4/6 inhibitor resistance, potentially through promotion of cyclin E or through inhibition of CDK inhibitor 1/CDK inhibitor 1B. Similarly oestrogen receptor (ER) signalling in ER-positive breast cancer might promote bypass of CDK4/6 inhibition, in part facilitated by cyclin D1 binding. b | Promising strategies for combinations of CDK4/6 inhibition with other antitumour agents, based on data from preclinical models, including blockade of ER signalling with tamoxifen, aromatase inhibitors or selective oestrogen-receptor degraders (SERDs), PI3K-pathway blockade with PI3K inhibitors and mTOR inhibition with rapamycin analogues, and MAPK pathway blockade with BRAF and MEK inhibitors. CKI; Cyclin-dependent kinase inhibitor.
Turner, N. C. et al. (2016) Treating cancer with selective CDK4/6 inhibitors Nat. Rev. Clin. Oncol. doi: /nrclinonc