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X Demographics
Mendeley readers
Attention Score in Context
| Title |
EGFR-Mediated Reactivation of MAPK Signaling Induces Acquired Resistance to GSK2118436 in BRAF V600E–Mutant NSCLC Cell Lines
|
|---|---|
| Published in |
Molecular Cancer Therapeutics, July 2016
|
| DOI | 10.1158/1535-7163.mct-15-0375 |
| Pubmed ID | |
| Authors |
Sung-Moo Kim, Hwan Kim, Kang Won Jang, Min Hwan Kim, Jinyoung Sohn, Mi Ran Yun, Han Na Kang, Chan Woo Kang, Hye Ryun Kim, Sun Min Lim, Yong Wha Moon, Joo Hang Kim, Soonmyung Paik, Byoung Chul Cho |
| Abstract |
Although treatment of BRAF V600E-mutant non-small cell lung cancer (NSCLCV600E) with GSK2118436 has shown an encouraging efficacy, most patients develop resistance. To investigate the mechanisms of acquired resistance to GSK2118436 in NSCLCV600E, we established GSK2118436-resistant (GSR) cells by exposing MV522 NSCLCV600E to increasing GSK2118436 concentrations. GSR cells displayed activated epidermal growth factor receptor (EGFR)-RAS-CRAF signaling with upregulated EGFR ligands and sustained activation of ERK1/2, but not MEK1/2, in the presence of GSK2118436. Treatment of GSR cells with GSK2118436 enhanced EGFR-mediated RAS activity, leading to the formation of BRAF-CRAF dimers and transactivation of CRAF. Interestingly, sustained activation of ERK1/2 was partly dependent on receptor-interacting protein kinase-2 (RIP2) activity but not on MEK1/2 activity. Combined BRAF and EGFR inhibition blocked reactivation of ERK signaling and improved efficacy in vitro and in vivo. Our findings support the evaluation of combined BRAF and EGFR inhibition in NSCLCV600E with acquired resistance to BRAF inhibitors. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Portugal | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 24 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 24 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 6 | 25% |
| Student > Master | 4 | 17% |
| Other | 3 | 13% |
| Student > Ph. D. Student | 1 | 4% |
| Student > Bachelor | 1 | 4% |
| Other | 2 | 8% |
| Unknown | 7 | 29% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 5 | 21% |
| Agricultural and Biological Sciences | 5 | 21% |
| Medicine and Dentistry | 3 | 13% |
| Unspecified | 1 | 4% |
| Social Sciences | 1 | 4% |
| Other | 1 | 4% |
| Unknown | 8 | 33% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. 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 20 May 2016.
All research outputs
#17,803,516
of 22,870,727 outputs
Outputs from Molecular Cancer Therapeutics
#3,230
of 3,864 outputs
Outputs of similar age
#256,196
of 355,044 outputs
Outputs of similar age from Molecular Cancer Therapeutics
#45
of 65 outputs
Altmetric has tracked 22,870,727 research outputs across all sources so far. This one is in the 19th percentile – i.e., 19% of other outputs scored the same or lower than it.
So far Altmetric has tracked 3,864 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.2. This one is in the 14th percentile – i.e., 14% of its peers scored the same or lower than it.
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 355,044 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 23rd percentile – i.e., 23% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 65 others from the same source and published within six weeks on either side of this one. This one is in the 26th percentile – i.e., 26% of its contemporaries scored the same or lower than it.