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24h-gene variation effect of combined bevacizumab/erlotinib in advanced non-squamous non-small cell lung cancer using exon array blood profiling

Overview of attention for article published in Journal of Translational Medicine, March 2017
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2 tweeters
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Title
24h-gene variation effect of combined bevacizumab/erlotinib in advanced non-squamous non-small cell lung cancer using exon array blood profiling
Published in
Journal of Translational Medicine, March 2017
DOI 10.1186/s12967-017-1174-z
Pubmed ID
Authors

Florent Baty, Markus Joerger, Martin Früh, Dirk Klingbiel, Francesco Zappa, Martin Brutsche

Abstract

The SAKK 19/05 trial investigated the safety and efficacy of the combined targeted therapy bevacizumab and erlotinib (BE) in unselected patients with advanced non-squamous non-small cell lung cancer (NSCLC). Although activating EGFR mutations were the strongest predictors of the response to BE, some patients not harboring driver mutations could benefit from the combined therapy. The identification of predictive biomarkers before or short after initiation of therapy is therefore paramount for proper patient selection, especially among EGFR wild-types. The first aim of this study was to investigate the early change in blood gene expression in unselected patients with advanced non-squamous NSCLC treated by BE. The second aim was to assess the predictive value of blood gene expression levels at baseline and 24h after BE therapy. Blood samples from 43 advanced non-squamous NSCLC patients taken at baseline and 24h after initiation of therapy were profiled using Affymetrix' exon arrays. The 24h gene dysregulation was investigated in the light of gene functional annotations using gene set enrichment analysis. The predictive value of blood gene expression levels was assessed and validated using an independent dataset. Significant gene dysregulations associated with the 24h-effect of BE were detected from blood-based whole-genome profiling. BE had a direct effect on "Pathways in cancer", by significantly down-regulating genes involved in cytokine-cytokine receptor interaction, MAPK signaling pathway and mTOR signaling pathway. These pathways contribute to phenomena of evasion of apoptosis, proliferation and sustained angiogenesis. Other signaling pathways specifically reflecting the mechanisms of action of erlotinib and the anti-angiogenesis effect of bevacizumab were activated. The magnitude of change of the most dysregulated genes at 24h did not have a predictive value regarding the patients' response to BE. However, predictive markers were identified from the gene expression levels at 24h regarding time to progression under BE. The 24h-effect of the combined targeted therapy BE could be accurately monitored in advanced non-squamous NSCLC blood samples using whole-genome exon arrays. Putative predictive markers at 24h could reflect patients' response to BE after adjusting for their mutational status. Trial registration ClinicalTrials.gov: NCT00354549.

Twitter Demographics

The data shown below were collected from the profiles of 2 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 12 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 12 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 4 33%
Student > Master 1 8%
Student > Ph. D. Student 1 8%
Other 1 8%
Student > Postgraduate 1 8%
Other 0 0%
Unknown 4 33%
Readers by discipline Count As %
Medicine and Dentistry 4 33%
Computer Science 1 8%
Agricultural and Biological Sciences 1 8%
Mathematics 1 8%
Unknown 5 42%

Attention Score in Context

This research output has an Altmetric Attention Score of 2. 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 15 August 2017.
All research outputs
#9,180,366
of 15,640,784 outputs
Outputs from Journal of Translational Medicine
#1,285
of 2,936 outputs
Outputs of similar age
#136,449
of 266,704 outputs
Outputs of similar age from Journal of Translational Medicine
#1
of 1 outputs
Altmetric has tracked 15,640,784 research outputs across all sources so far. This one is in the 39th percentile – i.e., 39% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,936 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.0. This one has gotten more attention than average, scoring higher than 50% 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 266,704 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 45th percentile – i.e., 45% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them