Imperial College London
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DrAlexisBarr

Faculty of Medicine, Institute of Clinical Sciences

Advanced Research Fellow
 
 
 
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Contact

 

+44 (0)20 7594 7772a.barr Website

 
 
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Location

 

Office 6.12BLMS BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Pennycook:2021:10.1098/rsob.210125,
author = {Pennycook, BR and Barr, AR},
doi = {10.1098/rsob.210125},
journal = {Open Biology},
title = {Palbociclib-mediated cell cycle arrest can occur in the absence of the CDK inhibitors p21 and p27},
url = {http://dx.doi.org/10.1098/rsob.210125},
volume = {11},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The use of CDK4/6 inhibitors in the treatment of a wide range of cancers is an area of ongoing investigation. Despite their increasing clinical use, there is limited understanding of the determinants of sensitivity and resistance to these drugs. Recent data have cast doubt on how CDK4/6 inhibitors arrest proliferation, provoking renewed interest in the role(s) of CDK4/6 in driving cell proliferation. As the use of CDK4/6 inhibitors in cancer therapies becomes more prominent, an understanding of their effect on the cell cycle becomes more urgent. Here, we investigate the mechanism of action of CDK4/6 inhibitors in promoting cell cycle arrest. Two main models explain how CDK4/6 inhibitors cause G1 cell cycle arrest, which differ in their dependence on the CDK inhibitor proteins p21 and p27. We have used live and fixed single-cell quantitative imaging, with inducible degradation systems, to address the roles of p21 and p27 in the mechanism of action of CDK4/6 inhibitors. We find that CDK4/6 inhibitors can initiate and maintain a cell cycle arrest without p21 or p27. This work clarifies our current understanding of the mechanism of action of CDK4/6 inhibitors and has implications for cancer treatment and patient stratification.
AU  - Pennycook,BR
AU  - Barr,AR
DO  - 10.1098/rsob.210125
PY  - 2021///
SN  - 2046-2441
TI  - Palbociclib-mediated cell cycle arrest can occur in the absence of the CDK inhibitors p21 and p27
T2  - Open Biology
UR  - http://dx.doi.org/10.1098/rsob.210125
UR  - http://hdl.handle.net/10044/1/92786
VL  - 11
ER  -
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