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Inhibiting EGF Receptor or SRC Family Kinase Signaling Overcomes BRAF Inhibitor Resistance in Melanoma

Overview of attention for article published in Cancer Discovery, December 2012
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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 (95th percentile)
  • High Attention Score compared to outputs of the same age and source (93rd percentile)

Mentioned by

news
1 news outlet
blogs
1 blog
twitter
7 tweeters
patent
12 patents

Citations

dimensions_citation
246 Dimensions

Readers on

mendeley
226 Mendeley
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Title
Inhibiting EGF Receptor or SRC Family Kinase Signaling Overcomes BRAF Inhibitor Resistance in Melanoma
Published in
Cancer Discovery, December 2012
DOI 10.1158/2159-8290.cd-12-0386
Pubmed ID
Authors

Maria R. Girotti, Malin Pedersen, Berta Sanchez-Laorden, Amaya Viros, Samra Turajlic, Dan Niculescu-Duvaz, Alfonso Zambon, John Sinclair, Andrew Hayes, Martin Gore, Paul Lorigan, Caroline Springer, James Larkin, Claus Jorgensen, Richard Marais

Abstract

We generated cell lines resistant to BRAF inhibitors and show that the EGF receptor (EGFR)-SRC family kinase (SFK)-STAT3 signaling pathway was upregulated in these cells. In addition to driving proliferation of resistant cells, this pathway also stimulated invasion and metastasis. EGFR inhibitors cooperated with BRAF inhibitors to block the growth of the resistant cells in vitro and in vivo, and monotherapy with the broad specificity tyrosine kinase inhibitor dasatinib blocked growth and metastasis in vivo. We analyzed tumors from patients with intrinsic or acquired resistance to vemurafenib and observed increased EGFR and SFK activity. Furthermore, dasatinib blocked the growth and metastasis of one of the resistant tumors in immunocompromised mice. Our data show that BRAF inhibitor-mediated activation of EGFR-SFK-STAT3 signaling can mediate resistance in patients with BRAF-mutant melanoma. We describe 2 treatments that seem to overcome this resistance and could deliver therapeutic efficacy in patients with drug-resistant BRAF-mutant melanoma.

Twitter Demographics

The data shown below were collected from the profiles of 7 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 226 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 5 2%
United Kingdom 3 1%
Germany 2 <1%
Austria 2 <1%
Netherlands 1 <1%
Switzerland 1 <1%
Korea, Republic of 1 <1%
Unknown 211 93%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 63 28%
Researcher 53 23%
Student > Master 18 8%
Student > Doctoral Student 14 6%
Student > Bachelor 14 6%
Other 39 17%
Unknown 25 11%
Readers by discipline Count As %
Agricultural and Biological Sciences 83 37%
Biochemistry, Genetics and Molecular Biology 61 27%
Medicine and Dentistry 36 16%
Pharmacology, Toxicology and Pharmaceutical Science 5 2%
Engineering 4 2%
Other 7 3%
Unknown 30 13%

Attention Score in Context

This research output has an Altmetric Attention Score of 26. 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 16 February 2021.
All research outputs
#911,651
of 17,356,510 outputs
Outputs from Cancer Discovery
#358
of 2,870 outputs
Outputs of similar age
#11,806
of 257,875 outputs
Outputs of similar age from Cancer Discovery
#3
of 48 outputs
Altmetric has tracked 17,356,510 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 94th percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 2,870 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 87% 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 257,875 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 48 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 93% of its contemporaries.