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Parallel RNA Interference Screens Identify EGFR Activation as an Escape Mechanism in FGFR3-Mutant Cancer

Overview of attention for article published in Cancer Discovery, June 2013
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (88th percentile)
  • Good Attention Score compared to outputs of the same age and source (79th percentile)

Mentioned by

blogs
1 blog
twitter
1 tweeter
patent
1 patent

Citations

dimensions_citation
81 Dimensions

Readers on

mendeley
83 Mendeley
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Title
Parallel RNA Interference Screens Identify EGFR Activation as an Escape Mechanism in FGFR3-Mutant Cancer
Published in
Cancer Discovery, June 2013
DOI 10.1158/2159-8290.cd-12-0569
Pubmed ID
Authors

Maria Teresa Herrera-Abreu, Alex Pearson, James Campbell, Steve D. Shnyder, Margaret A. Knowles, Alan Ashworth, Nicholas C. Turner

Abstract

Activation of fibroblast growth factor receptors (FGFR) is a common oncogenic event. Little is known about the determinants of sensitivity to FGFR inhibition and how these may vary between different oncogenic FGFRs. Using parallel RNA interference (RNAi) genetic screens, we show that the EGF receptor (EGFR) limits sensitivity to FGFR inhibition in FGFR3-mutant and -translocated cell lines, but not in other FGFR-driven cell lines. We also identify two distinct mechanisms through which EGFR limits sensitivity. In partially FGFR3-dependent lines, inhibition of FGFR3 results in transient downregulation of mitogen-activated protein kinase signaling that is rescued by rapid upregulation of EGFR signaling. In cell lines that are intrinsically resistant to FGFR inhibition, EGFR dominates signaling via repression of FGFR3, with EGFR inhibition rescued by delayed upregulation of FGFR3 expression. Importantly, combinations of FGFR and EGFR inhibitors overcome these resistance mechanisms in vitro and in vivo. Our results illustrate the power of parallel RNAi screens in identifying common resistance mechanisms to targeted therapies.

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

Geographical breakdown

Country Count As %
United States 2 2%
Austria 1 1%
Unknown 80 96%

Demographic breakdown

Readers by professional status Count As %
Researcher 29 35%
Student > Ph. D. Student 17 20%
Student > Master 10 12%
Other 5 6%
Student > Bachelor 4 5%
Other 11 13%
Unknown 7 8%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 27 33%
Agricultural and Biological Sciences 24 29%
Medicine and Dentistry 19 23%
Computer Science 1 1%
Immunology and Microbiology 1 1%
Other 1 1%
Unknown 10 12%

Attention Score in Context

This research output has an Altmetric Attention Score of 11. 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 17 January 2019.
All research outputs
#2,105,641
of 17,360,236 outputs
Outputs from Cancer Discovery
#666
of 2,885 outputs
Outputs of similar age
#32,124
of 271,162 outputs
Outputs of similar age from Cancer Discovery
#15
of 68 outputs
Altmetric has tracked 17,360,236 research outputs across all sources so far. Compared to these this one has done well and is in the 87th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 2,885 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 14.7. This one has done well, scoring higher than 76% 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 271,162 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 88% of its contemporaries.
We're also able to compare this research output to 68 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 79% of its contemporaries.