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Extreme Vulnerability of IDH1 Mutant Cancers to NAD+ Depletion

Overview of attention for article published in Cancer Cell, December 2015
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About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (97th percentile)
  • High Attention Score compared to outputs of the same age and source (84th percentile)

Mentioned by

news
7 news outlets
twitter
28 X users
patent
3 patents
googleplus
1 Google+ user
f1000
1 research highlight platform

Citations

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324 Dimensions

Readers on

mendeley
326 Mendeley
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Title
Extreme Vulnerability of IDH1 Mutant Cancers to NAD+ Depletion
Published in
Cancer Cell, December 2015
DOI 10.1016/j.ccell.2015.11.006
Pubmed ID
Authors

Kensuke Tateishi, Hiroaki Wakimoto, A. John Iafrate, Shota Tanaka, Franziska Loebel, Nina Lelic, Dmitri Wiederschain, Olivier Bedel, Gejing Deng, Bailin Zhang, Timothy He, Xu Shi, Robert E. Gerszten, Yiyun Zhang, Jing-Ruey J. Yeh, William T. Curry, Dan Zhao, Sudhandra Sundaram, Fares Nigim, Mara V.A. Koerner, Quan Ho, David E. Fisher, Elisabeth M. Roider, Lajos V. Kemeny, Yardena Samuels, Keith T. Flaherty, Tracy T. Batchelor, Andrew S. Chi, Daniel P. Cahill

Abstract

Heterozygous mutation of IDH1 in cancers modifies IDH1 enzymatic activity, reprogramming metabolite flux and markedly elevating 2-hydroxyglutarate (2-HG). Here, we found that 2-HG depletion did not inhibit growth of several IDH1 mutant solid cancer types. To identify other metabolic therapeutic targets, we systematically profiled metabolites in endogenous IDH1 mutant cancer cells after mutant IDH1 inhibition and discovered a profound vulnerability to depletion of the coenzyme NAD+. Mutant IDH1 lowered NAD+ levels by downregulating the NAD+ salvage pathway enzyme nicotinate phosphoribosyltransferase (Naprt1), sensitizing to NAD+ depletion via concomitant nicotinamide phosphoribosyltransferase (NAMPT) inhibition. NAD+ depletion activated the intracellular energy sensor AMPK, triggered autophagy, and resulted in cytotoxicity. Thus, we identify NAD+ depletion as a metabolic susceptibility of IDH1 mutant cancers.

X Demographics

X Demographics

The data shown below were collected from the profiles of 28 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 326 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 3 <1%
United States 3 <1%
Spain 2 <1%
Japan 2 <1%
Denmark 1 <1%
Sweden 1 <1%
Unknown 314 96%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 66 20%
Researcher 65 20%
Student > Master 36 11%
Student > Bachelor 29 9%
Other 18 6%
Other 63 19%
Unknown 49 15%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 89 27%
Agricultural and Biological Sciences 61 19%
Medicine and Dentistry 48 15%
Pharmacology, Toxicology and Pharmaceutical Science 19 6%
Neuroscience 9 3%
Other 38 12%
Unknown 62 19%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 70. 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 17 January 2021.
All research outputs
#614,394
of 25,432,721 outputs
Outputs from Cancer Cell
#463
of 3,153 outputs
Outputs of similar age
#10,121
of 395,714 outputs
Outputs of similar age from Cancer Cell
#7
of 39 outputs
Altmetric has tracked 25,432,721 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 97th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 3,153 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 37.3. This one has done well, scoring higher than 85% 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 395,714 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 97% of its contemporaries.
We're also able to compare this research output to 39 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 84% of its contemporaries.