↓ Skip to main content

Oncotarget

Article Metrics

Top2a identifies and provides epigenetic rationale for novel combination therapeutic strategies for aggressive prostate cancer

Overview of attention for article published in Oncotarget, December 2014
Altmetric Badge

Mentioned by

twitter
1 tweeter

Citations

dimensions_citation
46 Dimensions

Readers on

mendeley
38 Mendeley
Title
Top2a identifies and provides epigenetic rationale for novel combination therapeutic strategies for aggressive prostate cancer
Published in
Oncotarget, December 2014
DOI 10.18632/oncotarget.3077
Pubmed ID
Authors

Jason S. Kirk, Kevin Schaarschuch, Zafardjan Dalimov, Elena Lasorsa, ShengYu Ku, Swathi Ramakrishnan, Qiang Hu, Gissou Azabdaftari, Jianmin Wang, Roberto Pili, Leigh Ellis

Abstract

Progression of aggressive prostate cancers (PCa) with androgen receptor splice variants or neuroendrocrine features is currently untreatable in the clinic. Therefore novel therapies are urgently required. We conducted RNA-seq using tumors from a unique murine transplant mouse model which spontaneously progresses to metastatic disease. Differential gene expression analysis revealed a significant increase of topoisomerase IIα, Top2a (Top2a) in metastatic tumors. Interrogation of human data revealed that increased Top2a expression in primary tumors selected patients with more aggressive disease. Further, significant positive correlation was observed between Top2a and the histone methyltransferase, Ezh2. Combination of the Top2 poison etoposide with the Ezh2 inhibitor GSK126 or DZNep significantly increased cell death in vitro in murine and human prostate cancer cell lines. Additionally, combination therapy extended time to progression and increased therapeutic efficacy in vivo. Overall, our studies demonstrate that patients screened for Top2a and Ezh2 expression would exhibit significant response to a combinational treatment involving low dose etoposide combined with Ezh2 inhibition. In addition, our data suggests that this combination therapeutic strategy is beneficial against aggressive PCa, and provides strong rationale for continued clinical development.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 38 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 38 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 10 26%
Student > Ph. D. Student 6 16%
Student > Bachelor 5 13%
Student > Master 3 8%
Student > Doctoral Student 3 8%
Other 3 8%
Unknown 8 21%
Readers by discipline Count As %
Agricultural and Biological Sciences 7 18%
Biochemistry, Genetics and Molecular Biology 6 16%
Medicine and Dentistry 6 16%
Pharmacology, Toxicology and Pharmaceutical Science 2 5%
Computer Science 1 3%
Other 5 13%
Unknown 11 29%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 22 January 2015.
All research outputs
#14,675,892
of 16,638,522 outputs
Outputs from Oncotarget
#8,882
of 12,965 outputs
Outputs of similar age
#238,585
of 292,640 outputs
Outputs of similar age from Oncotarget
#158
of 266 outputs
Altmetric has tracked 16,638,522 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 12,965 research outputs from this source. They receive a mean Attention Score of 4.2. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 292,640 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 266 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.