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Resensitization to Crizotinib by the LorlatinibALKResistance Mutation L1198F

Overview of attention for article published in New England Journal of Medicine, January 2016
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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 (99th percentile)
  • Good Attention Score compared to outputs of the same age and source (76th percentile)

Mentioned by

news
9 news outlets
twitter
166 tweeters
facebook
6 Facebook pages

Citations

dimensions_citation
260 Dimensions

Readers on

mendeley
274 Mendeley
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Title
Resensitization to Crizotinib by the LorlatinibALKResistance Mutation L1198F
Published in
New England Journal of Medicine, January 2016
DOI 10.1056/nejmoa1508887
Pubmed ID
Authors

Alice T. Shaw, Luc Friboulet, Ignaty Leshchiner, Justin F. Gainor, Simon Bergqvist, Alexei Brooun, Benjamin J. Burke, Ya-Li Deng, Wei Liu, Leila Dardaei, Rosa L. Frias, Kate R. Schultz, Jennifer Logan, Leonard P. James, Tod Smeal, Sergei Timofeevski, Ryohei Katayama, A. John Iafrate, Long Le, Michele McTigue, Gad Getz, Ted W. Johnson, Jeffrey A. Engelman

Abstract

In a patient who had metastatic anaplastic lymphoma kinase (ALK)-rearranged lung cancer, resistance to crizotinib developed because of a mutation in the ALK kinase domain. This mutation is predicted to result in a substitution of cysteine by tyrosine at amino acid residue 1156 (C1156Y). Her tumor did not respond to a second-generation ALK inhibitor, but it did respond to lorlatinib (PF-06463922), a third-generation inhibitor. When her tumor relapsed, sequencing of the resistant tumor revealed an ALK L1198F mutation in addition to the C1156Y mutation. The L1198F substitution confers resistance to lorlatinib through steric interference with drug binding. However, L1198F paradoxically enhances binding to crizotinib, negating the effect of C1156Y and resensitizing resistant cancers to crizotinib. The patient received crizotinib again, and her cancer-related symptoms and liver failure resolved. (Funded by Pfizer and others; ClinicalTrials.gov number, NCT01970865 .).

Twitter Demographics

The data shown below were collected from the profiles of 166 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 274 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Japan 3 1%
United Kingdom 2 <1%
United States 2 <1%
Germany 2 <1%
Spain 1 <1%
Brazil 1 <1%
Czechia 1 <1%
Unknown 262 96%

Demographic breakdown

Readers by professional status Count As %
Researcher 74 27%
Student > Ph. D. Student 43 16%
Other 35 13%
Student > Master 24 9%
Student > Bachelor 20 7%
Other 51 19%
Unknown 27 10%
Readers by discipline Count As %
Medicine and Dentistry 99 36%
Biochemistry, Genetics and Molecular Biology 46 17%
Agricultural and Biological Sciences 45 16%
Pharmacology, Toxicology and Pharmaceutical Science 13 5%
Chemistry 12 4%
Other 17 6%
Unknown 42 15%

Attention Score in Context

This research output has an Altmetric Attention Score of 165. 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 26 September 2018.
All research outputs
#105,889
of 15,098,740 outputs
Outputs from New England Journal of Medicine
#2,697
of 26,709 outputs
Outputs of similar age
#3,192
of 366,049 outputs
Outputs of similar age from New England Journal of Medicine
#84
of 358 outputs
Altmetric has tracked 15,098,740 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 99th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 26,709 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 76.6. This one has done well, scoring higher than 89% 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 366,049 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 99% of its contemporaries.
We're also able to compare this research output to 358 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 76% of its contemporaries.