scholarly journals Combination of Abemaciclib following Eribulin Overcomes Palbociclib-Resistant Breast Cancer by Inhibiting the G2/M Cell Cycle Phase

Cancers ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 210
Author(s):  
Kamal Pandey ◽  
Nar Bahadur Katuwal ◽  
Nahee Park ◽  
Jin Hur ◽  
Young Bin Cho ◽  
...  

Breast cancer remains a leading cancer burden among women worldwide. Acquired resistance of cyclin-dependent kinase (CDK) 4/6 inhibitors occurs in almost all hormone receptor (HR)-positive subtype cases, comprising 70% of breast cancers, although CDK4/6 inhibitors combined with endocrine therapy are highly effective. CDK4/6 inhibitors are not expected to cooperate with cytotoxic chemotherapy based on the basic cytotoxic chemotherapy mode of action that inhibits rapidly proliferating cells. The palbociclib-resistant preclinical model developed in the current study investigated whether the combination of abemaciclib, CDK4/6 inhibitor with eribulin, an antimitotic chemotherapy could be a strategy to overcome palbociclib-resistant HR-positive breast cancer. The current study demonstrated that sequential abemaciclib treatment following eribulin synergistically suppressed CDK4/6 inhibitor-resistant cells by inhibiting the G2/M cell cycle phase more effectively. The current study showed the significant association of the pole-like kinase 1 (PLK1) level and palbociclib resistance. Moreover, the cumulative PLK1 inhibition in the G2/M phase by each eribulin or abemaciclib proved to be a mechanism of the synergistic effect. The synergistic antitumor effect was also supported by in vivo study. The sequential combination of abemaciclib following eribulin merits further clinical trials to overcome resistance to CDK4/6 inhibitors in HR-positive breast cancer.

2020 ◽  
Vol 31 (8) ◽  
pp. 845-857 ◽  
Author(s):  
Adrián E. Granada ◽  
Alba Jiménez ◽  
Jacob Stewart-Ornstein ◽  
Nils Blüthgen ◽  
Simone Reber ◽  
...  

DNA-damaging chemotherapy often leaves residual tumor cells. Combining single-cell long-term live imaging with information theory, we found an unexpected effect: highly proliferative cells were more likely to arrest than to die, whereas more slowly proliferating cells showed a higher probability of death.


2009 ◽  
Vol 100 (6) ◽  
pp. 959-970 ◽  
Author(s):  
M Loddo ◽  
S R Kingsbury ◽  
M Rashid ◽  
I Proctor ◽  
C Holt ◽  
...  

1990 ◽  
Vol 271 (1) ◽  
pp. 67-73 ◽  
Author(s):  
M J Hendzel ◽  
J R Davie

The incorporation of newly synthesized histones among various chromatin fraction isolated from non-replicating cell-cycle-phase-Go chicken immature erythrocytes was investigated. We find that newly synthesized erythroid-specific histone Hl variant H5, is incorporated randomly into chromatin. In contrast, newly synthesized nucleosomal histones H2A, H2A.Z, H2B, H3.3, and H4 are preferentially found in a fraction that is highly enriched in active/competent gene chromatin fragments and depleted in repressed gene chromatin. Moreover, ubiquitinated species of histones H2A and H2B and hyperacetylated species of H4 and H2B, which are complexed to active DNA, are labelled. These observations provide evidence that newly synthesized histones preferentially exchange with the nucleosomal histones of transcriptionally active/component chromatin domains. The results of this study suggest that nucleosomes of active chromatin may be inherently less stable than bulk nucleosomes in vivo and have implications for chromatin remodelling.


2012 ◽  
Vol 48 ◽  
pp. S143
Author(s):  
A. Szasz ◽  
F. Geszti ◽  
I. Zsákovics ◽  
B. Székely ◽  
A.M. Tokes ◽  
...  

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