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HER2 Overexpression Renders Human Breast Cancers Sensitive to PARP Inhibition Independently of Any Defect in Homologous Recombination DNA Repair

Overview of attention for article published in Cancer Research, September 2012
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About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (98th percentile)
  • High Attention Score compared to outputs of the same age and source (99th percentile)

Mentioned by

news
12 news outlets
blogs
1 blog
twitter
3 tweeters
patent
3 patents
googleplus
1 Google+ user

Citations

dimensions_citation
47 Dimensions

Readers on

mendeley
73 Mendeley
citeulike
1 CiteULike
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Title
HER2 Overexpression Renders Human Breast Cancers Sensitive to PARP Inhibition Independently of Any Defect in Homologous Recombination DNA Repair
Published in
Cancer Research, September 2012
DOI 10.1158/0008-5472.can-12-1287
Pubmed ID
Authors

Somaira Nowsheen, Tiffiny Cooper, James A. Bonner, Albert F. LoBuglio, Eddy S. Yang

Abstract

HER2 overexpression in breast cancer confers increased tumor aggressiveness. Although anti-HER2 therapies have improved patient outcome, resistance ultimately occurs. PARP inhibitors target homologous recombination (HR)-deficient tumors, such as the BRCA-associated breast and ovarian cancers. In this study, we show that HER2+ breast cancers are susceptible to PARP inhibition independent of an HR deficiency. HER2 overexpression in HER2 negative breast cancer cells was sufficient to render cells susceptible to the PARP inhibitors ABT-888 and AZD-2281 both in vitro and in vivo, which was abrogated by HER2 reduction. In addition, ABT-888 significantly inhibited NF-κB (p65/RelA) transcriptional activity in HER2+ but not HER2 negative breast cancer cells. This corresponded with a reduction in phosphorylated p65 and total IKKα levels, with a concomitant increase in IκBα. Overexpression of p65 abrogated cellular sensitivity to ABT-888, whereas IκBα overexpression reduced cell viability to a similar extent as ABT-888. Therefore, susceptibility of HER2+ breast cancer cells to PARP inhibition may be because of inhibition of NF-κB signaling driven by HER2. Our findings indicate that PARP inhibitors may be a novel therapeutic strategy for sporadic HER2+ breast cancer patients.

Twitter Demographics

The data shown below were collected from the profiles of 3 tweeters 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 73 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 1%
United States 1 1%
France 1 1%
Unknown 70 96%

Demographic breakdown

Readers by professional status Count As %
Researcher 18 25%
Student > Bachelor 10 14%
Student > Master 10 14%
Student > Ph. D. Student 9 12%
Student > Doctoral Student 3 4%
Other 9 12%
Unknown 14 19%
Readers by discipline Count As %
Agricultural and Biological Sciences 19 26%
Biochemistry, Genetics and Molecular Biology 14 19%
Medicine and Dentistry 13 18%
Pharmacology, Toxicology and Pharmaceutical Science 3 4%
Immunology and Microbiology 2 3%
Other 5 7%
Unknown 17 23%

Attention Score in Context

This research output has an Altmetric Attention Score of 100. 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 25 May 2022.
All research outputs
#319,810
of 21,415,362 outputs
Outputs from Cancer Research
#173
of 17,389 outputs
Outputs of similar age
#1,528
of 151,943 outputs
Outputs of similar age from Cancer Research
#1
of 150 outputs
Altmetric has tracked 21,415,362 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 98th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 17,389 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.4. This one has done particularly well, scoring higher than 99% 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 151,943 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 98% of its contemporaries.
We're also able to compare this research output to 150 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 99% of its contemporaries.