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Oncotarget

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
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44 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.

X Demographics

X Demographics

The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 44 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 44 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 10 23%
Student > Ph. D. Student 7 16%
Student > Bachelor 6 14%
Other 3 7%
Student > Doctoral Student 3 7%
Other 4 9%
Unknown 11 25%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 9 20%
Agricultural and Biological Sciences 7 16%
Medicine and Dentistry 6 14%
Pharmacology, Toxicology and Pharmaceutical Science 2 5%
Nursing and Health Professions 1 2%
Other 4 9%
Unknown 15 34%
Attention Score in Context

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 30 November 2022.
All research outputs
#18,071,805
of 23,221,875 outputs
Outputs from Oncotarget
#7,738
of 14,372 outputs
Outputs of similar age
#243,999
of 355,136 outputs
Outputs of similar age from Oncotarget
#180
of 323 outputs
Altmetric has tracked 23,221,875 research outputs across all sources so far. This one is in the 19th percentile – i.e., 19% of other outputs scored the same or lower than it.
So far Altmetric has tracked 14,372 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.7. This one is in the 40th percentile – i.e., 40% 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 355,136 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 27th percentile – i.e., 27% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 323 others from the same source and published within six weeks on either side of this one. This one is in the 39th percentile – i.e., 39% of its contemporaries scored the same or lower than it.