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Heterogeneous Mechanisms of Primary and Acquired Resistance to Third-Generation EGFR Inhibitors

Overview of attention for article published in Clinical Cancer Research, October 2016
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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 (87th percentile)
  • High Attention Score compared to outputs of the same age and source (80th percentile)

Mentioned by

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15 X users
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9 patents
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1 Facebook page

Citations

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224 Dimensions

Readers on

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128 Mendeley
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Title
Heterogeneous Mechanisms of Primary and Acquired Resistance to Third-Generation EGFR Inhibitors
Published in
Clinical Cancer Research, October 2016
DOI 10.1158/1078-0432.ccr-15-1915
Pubmed ID
Authors

Sandra Ortiz-Cuaran, Matthias Scheffler, Dennis Plenker, llona Dahmen, Andreas H. Scheel, Lynnette Fernandez-Cuesta, Lydia Meder, Christine M. Lovly, Thorsten Persigehl, Sabine Merkelbach-Bruse, Marc Bos, Sebastian Michels, Rieke Fischer, Kerstin Albus, Katharina König, Hans-Ulrich Schildhaus, Jana Fassunke, Michaela A. Ihle, Helen Pasternack, Carina Heydt, Christian Becker, Janine Altmüller, Hongbin Ji, Christian Müller, Alexandra Florin, Johannes M. Heuckmann, Peter Nuernberg, Sascha Ansén, Lukas C. Heukamp, Johannes Berg, William Pao, Martin Peifer, Reinhard Buettner, Jürgen Wolf, Roman K. Thomas, Martin L. Sos

Abstract

To identify novel mechanisms of resistance to third-generation EGFR inhibitors in lung adenocarcinoma patients that progressed under therapy with either AZD9291 or rociletinib (CO-1686). We analyzed tumor biopsies from seven patients obtained before, during and/or after treatment with AZD9291or rociletinib (CO-1686). Targeted sequencing and FISH analyses were performed and the relevance of candidate genes was functionally assessed in in vitro models. We found recurrent amplification of either MET or ERBB2 in tumors that were resistant or developed resistance to third-generation EGFR inhibitors and show that ERBB2 and MET activation can confer resistance to these compounds. Furthermore, we identified a KRASG12S mutation in a patient with acquired resistance to AZD9291 as a potential driver of acquired resistance. Finally, we show that dual inhibition of EGFR/MEK might be a viable strategy to overcome resistance in EGFR-mutant cells expressing mutant KRAS. Our data suggests that heterogeneous mechanisms of resistance can drive primary and acquired resistance to third-generation EGFR inhibitors and provides a rationale for potential combination strategies.

X Demographics

X Demographics

The data shown below were collected from the profiles of 15 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 128 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 <1%
Unknown 127 99%

Demographic breakdown

Readers by professional status Count As %
Researcher 31 24%
Student > Ph. D. Student 17 13%
Student > Master 14 11%
Other 12 9%
Student > Bachelor 10 8%
Other 15 12%
Unknown 29 23%
Readers by discipline Count As %
Medicine and Dentistry 27 21%
Biochemistry, Genetics and Molecular Biology 27 21%
Agricultural and Biological Sciences 21 16%
Pharmacology, Toxicology and Pharmaceutical Science 6 5%
Chemistry 4 3%
Other 8 6%
Unknown 35 27%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 14. 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 14 November 2023.
All research outputs
#2,298,340
of 23,680,154 outputs
Outputs from Clinical Cancer Research
#1,918
of 12,801 outputs
Outputs of similar age
#40,933
of 325,798 outputs
Outputs of similar age from Clinical Cancer Research
#31
of 153 outputs
Altmetric has tracked 23,680,154 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 90th percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 12,801 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 11.2. This one has done well, scoring higher than 84% 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 325,798 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 87% of its contemporaries.
We're also able to compare this research output to 153 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 80% of its contemporaries.