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Review
. 2018 Jul 9;34(1):9-20.
doi: 10.1016/j.ccell.2018.03.023. Epub 2018 May 3.

CDK4/6 Inhibitors: The Mechanism of Action May Not Be as Simple as Once Thought

Mary E Klein  1 , Marta Kovatcheva  1 , Lara E Davis  2 , William D Tap  3 , Andrew Koff  4
Affiliations
Review

CDK4/6 Inhibitors: The Mechanism of Action May Not Be as Simple as Once Thought

Mary E Klein et al. Cancer Cell. .

Abstract

CDK4/6 inhibitors are among a new generation of therapeutics. Building upon the striking success of the combination of CDK4/6 inhibitors and the hormone receptor antagonist letrozole in breast cancer, many other combinations have recently entered clinical trials in multiple diseases. To achieve maximal benefit with CDK4/6 inhibitors it will be critical to understand the cellular mechanisms by which they act. Here we highlight the mechanisms by which CDK4/6 inhibitors can exert their anti-tumor activities beyond simply enforcing cytostatic growth arrest, and discuss how this knowledge may inform new combinations, improve outcomes, and modify dosing schedules in the future.

Keywords: CDK4/6 inhibitors; abemaciclib; metabolism; palbociclib; ribociclib; senescence; tumor microenvironment.

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Figures

Figure 1
Figure 1. The consequences of CDK4/6 inhibition
The four cellular mechanisms, labeled A-D, that contribute to the efficacy of CDK4/6 inhibitors are shown. Details are in the accompanying text.
See this image and copyright information in PMC

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