Palbociclib-mediated cell cycle arrest can occur in the absence of the CDK inhibitors p21 and p27

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 a...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Betheney R. Pennycook, Alexis R. Barr
Formato:	article
Lenguaje:	EN
Publicado:	The Royal Society 2021
Materias:	cell cycle proliferation cancer biology cyclin-dependent kinases Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/0c9ea1421674436780d21724cf39f9ba
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:0c9ea1421674436780d21724cf39f9ba
record_format	dspace
spelling	oai:doaj.org-article:0c9ea1421674436780d21724cf39f9ba2021-11-17T08:06:15ZPalbociclib-mediated cell cycle arrest can occur in the absence of the CDK inhibitors p21 and p2710.1098/rsob.2101252046-2441https://doaj.org/article/0c9ea1421674436780d21724cf39f9ba2021-11-01T00:00:00Zhttps://royalsocietypublishing.org/doi/10.1098/rsob.210125https://doaj.org/toc/2046-2441The 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.Betheney R. PennycookAlexis R. BarrThe Royal Societyarticlecell cycleproliferationcancer biologycyclin-dependent kinasesBiology (General)QH301-705.5ENOpen Biology, Vol 11, Iss 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cell cycle proliferation cancer biology cyclin-dependent kinases Biology (General) QH301-705.5
spellingShingle	cell cycle proliferation cancer biology cyclin-dependent kinases Biology (General) QH301-705.5 Betheney R. Pennycook Alexis R. Barr Palbociclib-mediated cell cycle arrest can occur in the absence of the CDK inhibitors p21 and p27
description	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.
format	article
author	Betheney R. Pennycook Alexis R. Barr
author_facet	Betheney R. Pennycook Alexis R. Barr
author_sort	Betheney R. Pennycook
title	Palbociclib-mediated cell cycle arrest can occur in the absence of the CDK inhibitors p21 and p27
title_short	Palbociclib-mediated cell cycle arrest can occur in the absence of the CDK inhibitors p21 and p27
title_full	Palbociclib-mediated cell cycle arrest can occur in the absence of the CDK inhibitors p21 and p27
title_fullStr	Palbociclib-mediated cell cycle arrest can occur in the absence of the CDK inhibitors p21 and p27
title_full_unstemmed	Palbociclib-mediated cell cycle arrest can occur in the absence of the CDK inhibitors p21 and p27
title_sort	palbociclib-mediated cell cycle arrest can occur in the absence of the cdk inhibitors p21 and p27
publisher	The Royal Society
publishDate	2021
url	https://doaj.org/article/0c9ea1421674436780d21724cf39f9ba
work_keys_str_mv	AT betheneyrpennycook palbociclibmediatedcellcyclearrestcanoccurintheabsenceofthecdkinhibitorsp21andp27 AT alexisrbarr palbociclibmediatedcellcyclearrestcanoccurintheabsenceofthecdkinhibitorsp21andp27
_version_	1718425779588562944

Palbociclib-mediated cell cycle arrest can occur in the absence of the CDK inhibitors p21 and p27

Ejemplares similares