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Cancer Cell. 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.

Author information

1
The Louis V. Gerstner Graduate School of Biomedical Sciences and the Sloan Kettering Institute Program in Molecular Biology, Memorial Sloan Kettering Cancer Center, RRL917C, Box 207, 1275 York Avenue, New York, NY 10065, USA.
2
Knight Cancer Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.
3
Departments of Medicine at Memorial Sloan Kettering Cancer Center and the Weill Cornell College of Medicine, 1275 York Avenue, New York, NY 10065, USA.
4
The Louis V. Gerstner Graduate School of Biomedical Sciences and the Sloan Kettering Institute Program in Molecular Biology, Memorial Sloan Kettering Cancer Center, RRL917C, Box 207, 1275 York Avenue, New York, NY 10065, USA. Electronic address: koffa@mskcc.org.

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

PMID:
29731395
PMCID:
PMC6039233
DOI:
10.1016/j.ccell.2018.03.023
[Indexed for MEDLINE]
Free PMC Article

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