CDK4/6 inhibitors: The mechanism of action may not be as simple as once thought Journal Article
| Authors: | Klein, M. E.; Kovatcheva, M.; Davis, L. E.; Tap, W. D.; Koff, A. |
| Article Title: | CDK4/6 inhibitors: The mechanism of action may not be as simple as once thought |
| 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. © 2018 Elsevier Inc. 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: | signal transduction; unclassified drug; clinical trial; review; nonhuman; antineoplastic agent; metabolism; antineoplastic activity; cell cycle arrest; senescence; cyclin dependent kinase inhibitor; cell metabolism; cell aging; cytostasis; cytostatic agent; tumor microenvironment; human; priority journal; palbociclib; cyclin dependent kinase 4 inhibitor; abemaciclib; ribociclib; cdk4/6 inhibitors; cyclin dependent kinase 6 inhibitor |
| Journal Title: | Cancer Cell |
| Volume: | 34 |
| Issue: | 1 |
| ISSN: | 1535-6108 |
| Publisher: | Cell Press |
| Date Published: | 2018-07-09 |
| Start Page: | 9 |
| End Page: | 20 |
| Language: | English |
| DOI: | 10.1016/j.ccell.2018.03.023 |
| PROVIDER: | scopus |
| PMCID: | PMC6039233 |
| PUBMED: | 29731395 |
| DOI/URL: | |
| Notes: | Review -- Export Date: 1 August 2018 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
Related MSK Work