↓ Skip to main content

ETS‐targeted therapy: can it substitute for MEK inhibitors?

Overview of attention for article published in Clinical and Translational Medicine, May 2017
Altmetric Badge

Mentioned by

twitter
2 tweeters

Citations

dimensions_citation
14 Dimensions

Readers on

mendeley
37 Mendeley
You are seeing a free-to-access but limited selection of the activity Altmetric has collected about this research output. Click here to find out more.
Title
ETS‐targeted therapy: can it substitute for MEK inhibitors?
Published in
Clinical and Translational Medicine, May 2017
DOI 10.1186/s40169-017-0147-4
Pubmed ID
Authors

Osamu Tetsu, Frank McCormick

Abstract

The RAS/MAPK pathway has been intensively studied in cancer. Constitutive activation of ERK1 and ERK2 is frequently found in cancer cells from a variety of tissues. In clinical practice and clinical trials, small molecules targeting receptor tyrosine kinases or components in the MAPK cascade are used for treatment. MEK1 and MEK2 are ideal targets because these enzymes are physiologically important and have narrow substrate specificities and distinctive structural characteristics. Despite success in pre-clinical testing, only two MEK inhibitors, trametinib and cobimetinib, have been approved, both for treatment of BRAF-mutant melanoma. Surprisingly, the efficacy of MEK inhibitors in other tumors has been disappointing. These facts suggest the need for a different approach. We here consider transcription factor ETS1 and ETS2 as alternate therapeutic targets because they are major MAPK downstream effectors. The lack of clinical efficacy of MEK inhibitors is attributed mostly to a subsequent loss of negative feedback regulation in the MAPK pathway. To overcome this obstacle, second-generation MEK inhibitors, so-called "feedback busters," have been developed. However, their efficacy is still unsatisfactory in the majority of cancers. To substitute ETS-targeted therapy, therapeutic strategies to modulate the transcription factor in cancer must be considered. Chemical targeting of ETS1 for proteolysis is a promising strategy; Src and USP9X inhibitors might achieve this by accelerating ETS1 protein turnover. Targeting the ETS1 interface might have great therapeutic value because ETS1 dimerizes itself or with other transcription factors to regulate target genes. In addition, transcriptional cofactors, including CBP/p300 and BRD4, represent intriguing targets for both ETS1 and ETS2. ETS-targeted therapy appears to be promising. However, it may have a potential problem. It might inhibit autoregulatory negative feedback loops in the MAPK pathway, with consequent resistance to cell death by ERK1 and ERK2 activation. Further research is warranted to explore clinically applicable ways to inhibit ETS1 and ETS2.

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 37 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Canada 1 3%
Unknown 36 97%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 11 30%
Student > Bachelor 5 14%
Researcher 5 14%
Other 5 14%
Student > Master 3 8%
Other 3 8%
Unknown 5 14%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 12 32%
Medicine and Dentistry 5 14%
Immunology and Microbiology 3 8%
Agricultural and Biological Sciences 3 8%
Chemistry 3 8%
Other 3 8%
Unknown 8 22%

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 10 May 2017.
All research outputs
#11,758,410
of 15,414,285 outputs
Outputs from Clinical and Translational Medicine
#160
of 243 outputs
Outputs of similar age
#180,107
of 267,119 outputs
Outputs of similar age from Clinical and Translational Medicine
#1
of 1 outputs
Altmetric has tracked 15,414,285 research outputs across all sources so far. This one is in the 20th percentile – i.e., 20% of other outputs scored the same or lower than it.
So far Altmetric has tracked 243 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.9. This one is in the 32nd percentile – i.e., 32% 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 267,119 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 27th percentile – i.e., 27% 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