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EGFR-Mediated Reactivation of MAPK Signaling Contributes to Insensitivity of BRAF-Mutant Colorectal Cancers to RAF Inhibition with Vemurafenib

Overview of attention for article published in Cancer Discovery, January 2012
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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 (#30 of 3,147)
  • High Attention Score compared to outputs of the same age (99th percentile)
  • High Attention Score compared to outputs of the same age and source (99th percentile)

Citations

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662 Dimensions

Readers on

mendeley
419 Mendeley
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1 CiteULike
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Title
EGFR-Mediated Reactivation of MAPK Signaling Contributes to Insensitivity of BRAF-Mutant Colorectal Cancers to RAF Inhibition with Vemurafenib
Published in
Cancer Discovery, January 2012
DOI 10.1158/2159-8290.cd-11-0341
Pubmed ID
Authors

Ryan B. Corcoran, Hiromichi Ebi, Alexa B. Turke, Erin M. Coffee, Michiya Nishino, Alexandria P. Cogdill, Ronald D. Brown, Patricia Della Pelle, Dora Dias-Santagata, Kenneth E. Hung, Keith T. Flaherty, Adriano Piris, Jennifer A. Wargo, Jeffrey Settleman, Mari Mino-Kenudson, Jeffrey A. Engelman

Abstract

BRAF mutations occur in 10-15% of colorectal cancers (CRCs) and confer adverse outcome. While RAF inhibitors such as vemurafenib (PLX4032) have proven effective in BRAF mutant melanoma, they are surprisingly ineffective in BRAF mutant CRCs, and the reason for this disparity remains unclear. Compared to BRAF mutant melanoma cells, BRAF mutant CRC cells were less sensitive to vemurafenib, and P-ERK suppression was not sustained in response to treatment. Although transient inhibition of phospho-ERK by vemurafenib was observed in CRC, rapid ERK re-activation occurred through EGFR-mediated activation of RAS and CRAF. BRAF mutant CRCs expressed higher levels of phospho-EGFR than BRAF mutant melanomas, suggesting that CRCs are specifically poised for EGFR-mediated resistance. Combined RAF and EGFR inhibition blocked reactivation of MAPK signaling in BRAF mutant CRC cells and markedly improved efficacy in vitro and in vivo. These findings support evaluation of combined RAF and EGFR inhibition in BRAF mutant CRC patients.

Twitter Demographics

The data shown below were collected from the profiles of 8 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 419 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Germany 2 <1%
Netherlands 2 <1%
United Kingdom 2 <1%
Italy 1 <1%
Korea, Republic of 1 <1%
Spain 1 <1%
United States 1 <1%
Unknown 409 98%

Demographic breakdown

Readers by professional status Count As %
Researcher 107 26%
Student > Ph. D. Student 92 22%
Student > Master 39 9%
Student > Bachelor 30 7%
Student > Doctoral Student 29 7%
Other 74 18%
Unknown 48 11%
Readers by discipline Count As %
Agricultural and Biological Sciences 134 32%
Medicine and Dentistry 100 24%
Biochemistry, Genetics and Molecular Biology 93 22%
Pharmacology, Toxicology and Pharmaceutical Science 11 3%
Chemistry 9 2%
Other 21 5%
Unknown 51 12%

Attention Score in Context

This research output has an Altmetric Attention Score of 201. 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 21 October 2021.
All research outputs
#121,961
of 19,458,329 outputs
Outputs from Cancer Discovery
#30
of 3,147 outputs
Outputs of similar age
#489
of 137,507 outputs
Outputs of similar age from Cancer Discovery
#1
of 43 outputs
Altmetric has tracked 19,458,329 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 3,147 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 16.8. This one has done particularly well, scoring higher than 99% 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 137,507 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 43 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 99% of its contemporaries.