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Trastuzumab-Resistant HER2+ Breast Cancer Cells Retain Sensitivity to Poly (ADP-Ribose) Polymerase (PARP) Inhibition

Overview of attention for article published in Molecular Cancer Therapeutics, April 2018
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About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • Among the highest-scoring outputs from this source (#40 of 3,701)
  • High Attention Score compared to outputs of the same age (96th percentile)
  • High Attention Score compared to outputs of the same age and source (96th percentile)

Mentioned by

news
11 news outlets
twitter
4 tweeters

Citations

dimensions_citation
7 Dimensions

Readers on

mendeley
24 Mendeley
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Title
Trastuzumab-Resistant HER2+ Breast Cancer Cells Retain Sensitivity to Poly (ADP-Ribose) Polymerase (PARP) Inhibition
Published in
Molecular Cancer Therapeutics, April 2018
DOI 10.1158/1535-7163.mct-17-0302
Pubmed ID
Authors

Monica E. Wielgos, Zhuo Zhang, Rajani Rajbhandari, Tiffiny S. Cooper, Ling Zeng, Andres Forero, Francisco J. Esteva, C. Kent Osborne, Rachel Schiff, Albert F. LoBuglio, Susan E. Nozell, Eddy S. Yang

Abstract

HER2-targeted therapies, such as trastuzumab, have increased the survival rates of HER2+ breast cancer patients. However, despite these therapies, many tumors eventually develop resistance to these therapies. Our lab previously reported an unexpected sensitivity of HER2+ breast cancer cells to poly (ADP-Ribose) polymerase inhibitors (PARPi), agents that target homologous recombination (HR) deficient tumors, independent of a DNA repair deficiency. In this study, we investigated whether HER2+ trastuzumab resistant (TR) breast cancer cells were susceptible to PARPi and the mechanism behind PARPi induced cytotoxicity. We demonstrate that the PARPi ABT-888 (veliparib) decreased cell survival in-vitro and tumor growth in vivo of HER2+ trastuzumab resistant breast cancer cells. PARP-1 siRNA confirmed that cytotoxicity was due, in part, to PARP-1 inhibition. Furthermore, PARP-1 silencing had variable effects on the expression of several NF-κB-regulated genes. In particular, silencing PARP-1 inhibited NF-κB activity and reduced p65 binding at the IL-8 promoter, which resulted in a decrease in IL-8 mRNA and protein expression. Our results provide insight in the potential mechanism by which PARPi induces cytotoxicity in HER2+ breast cancer cells and support the testing of PARPi in patients with HER2+ breast cancer resistant to trastuzumab.

Twitter Demographics

The data shown below were collected from the profiles of 4 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 24 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 24 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 3 13%
Researcher 3 13%
Student > Ph. D. Student 3 13%
Student > Postgraduate 2 8%
Lecturer 1 4%
Other 3 13%
Unknown 9 38%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 3 13%
Medicine and Dentistry 3 13%
Chemistry 3 13%
Pharmacology, Toxicology and Pharmaceutical Science 2 8%
Economics, Econometrics and Finance 1 4%
Other 3 13%
Unknown 9 38%

Attention Score in Context

This research output has an Altmetric Attention Score of 82. 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
#396,878
of 21,415,362 outputs
Outputs from Molecular Cancer Therapeutics
#40
of 3,701 outputs
Outputs of similar age
#10,542
of 298,166 outputs
Outputs of similar age from Molecular Cancer Therapeutics
#2
of 50 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 3,701 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 7.9. This one has done particularly well, scoring higher than 98% 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 298,166 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 96% of its contemporaries.
We're also able to compare this research output to 50 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 96% of its contemporaries.