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The Unpluggable in Pursuit of the Undruggable: Tackling the Dark Matter of the Cancer Therapeutics Universe

Overview of attention for article published in Frontiers in oncology, January 2013
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Title
The Unpluggable in Pursuit of the Undruggable: Tackling the Dark Matter of the Cancer Therapeutics Universe
Published in
Frontiers in oncology, January 2013
DOI 10.3389/fonc.2013.00304
Pubmed ID
Authors

Richard J. Epstein

Abstract

The notion that targeted drugs can unplug gain-of-function tumor pathways has revitalized pharmaceutical research, but the survival benefits of this strategy have so far proven modest. A weakness of oncogene-blocking approaches is that they do not address the problem of cancer progression as selected by the recessive phenotypes of genetic instability and apoptotic resistance which in turn arise from loss-of-function - i.e., undruggable - defects of caretaker (e.g., BRCA, MLH1) or gatekeeper (e.g., TP53, PTEN) suppressor genes. Genetic instability ensures that rapid cell kill is balanced by rapid selection for apoptotic resistance and hence for metastasis, casting doubt on the assumption that cytotoxicity ("response") remains the best way to identify survival-enhancing drugs. In the absence of gene therapy, it is proposed here that caretaker-defective (high-instability) tumors may be best treated with low-lethality drugs inducing replicative (RAS-RAF-ERK) arrest or dormancy, causing "stable disease" rather than tumorilytic remission. Gatekeeper-defective (death-resistant) tumors, on the other hand, may be best managed by combining survival (PI3K-AKT-mTOR) pathway blockade with metronomic or sequential pro-apoptotic drugs.

X Demographics

X Demographics

The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 29 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 3%
Japan 1 3%
Denmark 1 3%
Unknown 26 90%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 8 28%
Student > Bachelor 5 17%
Researcher 4 14%
Student > Postgraduate 2 7%
Professor > Associate Professor 2 7%
Other 5 17%
Unknown 3 10%
Readers by discipline Count As %
Agricultural and Biological Sciences 10 34%
Medicine and Dentistry 6 21%
Biochemistry, Genetics and Molecular Biology 4 14%
Pharmacology, Toxicology and Pharmaceutical Science 2 7%
Chemistry 2 7%
Other 2 7%
Unknown 3 10%
Attention Score in Context

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 12 December 2013.
All research outputs
#19,945,185
of 25,374,917 outputs
Outputs from Frontiers in oncology
#9,321
of 22,416 outputs
Outputs of similar age
#221,306
of 289,007 outputs
Outputs of similar age from Frontiers in oncology
#142
of 328 outputs
Altmetric has tracked 25,374,917 research outputs across all sources so far. This one is in the 18th percentile – i.e., 18% of other outputs scored the same or lower than it.
So far Altmetric has tracked 22,416 research outputs from this source. They receive a mean Attention Score of 3.0. This one is in the 49th percentile – i.e., 49% 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 289,007 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 20th percentile – i.e., 20% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 328 others from the same source and published within six weeks on either side of this one. This one is in the 45th percentile – i.e., 45% of its contemporaries scored the same or lower than it.