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Molecular determinants of drug-specific sensitivity for epidermal growth factor receptor (EGFR) exon 19 and 20 mutants in non-small cell lung cancer

Overview of attention for article published in Oncotarget, February 2015
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  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (95th percentile)
  • High Attention Score compared to outputs of the same age and source (98th percentile)

Mentioned by

news
5 news outlets
twitter
4 tweeters
reddit
1 Redditor

Citations

dimensions_citation
18 Dimensions

Readers on

mendeley
35 Mendeley
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Title
Molecular determinants of drug-specific sensitivity for epidermal growth factor receptor (EGFR) exon 19 and 20 mutants in non-small cell lung cancer
Published in
Oncotarget, February 2015
DOI 10.18632/oncotarget.3472
Pubmed ID
Authors

Igor F. Tsigelny, Jennifer J. Wheler, Jerry P. Greenberg, Valentina L. Kouznetsova, David J. Stewart, Lyudmila Bazhenova, Razelle Kurzrock

Abstract

We hypothesized that aberrations activating epidermal growth factor receptor (EGFR) via dimerization would be more sensitive to anti-dimerization agents (e.g., cetuximab). EGFR exon 19 abnormalities (L747_A750del; deletes amino acids LREA) respond to reversible EGFR kinase inhibitors (TKIs). Exon 20 in-frame insertions and/or duplications (codons 767 to 774) and T790M mutations are clinically resistant to reversible/some irreversible TKIs. Their impact on protein function/therapeutic actionability are not fully elucidated.In our study, the index patient with non-small cell lung cancer (NSCLC) harbored EGFR D770_P772del_insKG (exon 20). A twenty patient trial (NSCLC cohort) (cetuximab-based regimen) included two participants with EGFR TKI-resistant mutations ((i) exon 20 D770>GY; and (ii) exon 19 LREA plus exon 20 T790M mutations). Structural modeling predicted that EGFR exon 20 anomalies (D770_P772del_insKG and D770>GY), but not T790M mutations, stabilize the active dimer configuration by increasing the interaction between the kinase domains, hence sensitizing to an agent preventing dimerization. Consistent with predictions, the two patients harboring D770_P772del_insKG and D770>GY, respectively, responded to an EGFR antibody (cetuximab)-based regimen; the T790M-bearing patient showed no response to cetuximab combined with erlotinib. In silico modeling merits investigation of its ability to optimize therapeutic selection based on structural/functional implications of different aberrations within the same gene.

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

Geographical breakdown

Country Count As %
Sweden 1 3%
Unknown 34 97%

Demographic breakdown

Readers by professional status Count As %
Researcher 8 23%
Student > Ph. D. Student 5 14%
Student > Master 4 11%
Professor 4 11%
Student > Postgraduate 3 9%
Other 8 23%
Unknown 3 9%
Readers by discipline Count As %
Medicine and Dentistry 13 37%
Agricultural and Biological Sciences 5 14%
Biochemistry, Genetics and Molecular Biology 5 14%
Pharmacology, Toxicology and Pharmaceutical Science 2 6%
Computer Science 2 6%
Other 4 11%
Unknown 4 11%

Attention Score in Context

This research output has an Altmetric Attention Score of 42. 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 10 July 2020.
All research outputs
#566,404
of 16,562,219 outputs
Outputs from Oncotarget
#224
of 12,955 outputs
Outputs of similar age
#9,988
of 226,893 outputs
Outputs of similar age from Oncotarget
#5
of 367 outputs
Altmetric has tracked 16,562,219 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 96th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 12,955 research outputs from this source. They receive a mean Attention Score of 4.2. 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 226,893 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 95% of its contemporaries.
We're also able to compare this research output to 367 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 98% of its contemporaries.