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Combinatorial antitumor effect of HDACs and the PI3K-Akt-mTOR pathway inhibition in a Pten deficient model of prostate cancer

Overview of attention for article published in Oncotarget, September 2013
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1 tweeter

Citations

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55 Dimensions

Readers on

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42 Mendeley
Title
Combinatorial antitumor effect of HDACs and the PI3K-Akt-mTOR pathway inhibition in a Pten deficient model of prostate cancer
Published in
Oncotarget, September 2013
DOI 10.18632/oncotarget.1314
Pubmed ID
Authors

Leigh Ellis, ShengYu Ku, Swathi Ramakrishnan, Elena Lasorsa, Gizzou Azabdaftari, Alejandro Godoy, Roberto Pili

Abstract

Increased expression of histone deacetylases (HDACs) and activation of the PI3K-Akt-mTORC1 pathway are common aberrations in prostate cancer (PCa). For this reason, inhibition of such targets is an exciting avenue for the development of novel therapeutic strategies to treat patients with advanced PCa. Previous reports demonstrated that HDAC inhibitors (HDACi) increases DNA damage and induce greater apoptosis in PCa cell lines that express androgen receptor (AR). In this study we utilized the AR negative PCa cell line and observed that re-expression of AR (PC3-AR) results in greater levels of apoptosis when treated with the pan-DACi, panobinostat (PAN). PAN mediated apoptosis in PC3 and PC3-AR cells was associated with increased levels of double strand DNA breaks, indicated by p-ɣH2AX. Further, PAN treatment in PC3-AR cells resulted in moderate attenuation of the ATM-Akt-ERK DNA damage response pathway. For this reason, we combined PAN with the dual PI3K-mTOR inhibitor, BEZ235. Combination of PAN with BEZ235 resulted in significant attenuation of the DNA damage repair protein ATM and significantly increased anti-tumor activity compared to each single treatment. Overall, superior anti-tumor activity with combination of PAN with BEZ235 was independent of AR status. These findings suggest that this therapeutic strategy should be further developed in clinical trials.

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 42 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 2%
Unknown 41 98%

Demographic breakdown

Readers by professional status Count As %
Researcher 10 24%
Student > Ph. D. Student 7 17%
Student > Bachelor 5 12%
Student > Master 4 10%
Student > Doctoral Student 3 7%
Other 8 19%
Unknown 5 12%
Readers by discipline Count As %
Agricultural and Biological Sciences 14 33%
Medicine and Dentistry 10 24%
Biochemistry, Genetics and Molecular Biology 7 17%
Unspecified 1 2%
Computer Science 1 2%
Other 2 5%
Unknown 7 17%

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 31 October 2013.
All research outputs
#9,572,955
of 15,042,885 outputs
Outputs from Oncotarget
#4,329
of 12,689 outputs
Outputs of similar age
#104,423
of 186,617 outputs
Outputs of similar age from Oncotarget
#10
of 24 outputs
Altmetric has tracked 15,042,885 research outputs across all sources so far. This one is in the 23rd percentile – i.e., 23% of other outputs scored the same or lower than it.
So far Altmetric has tracked 12,689 research outputs from this source. They receive a mean Attention Score of 4.0. This one has gotten more attention than average, scoring higher than 56% of its peers.
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 186,617 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 33rd percentile – i.e., 33% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 24 others from the same source and published within six weeks on either side of this one. This one is in the 45th percentile – i.e., 45% of its contemporaries scored the same or lower than it.