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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 (82nd percentile)

Citations

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122 Dimensions

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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.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 190 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 3 2%
United States 3 2%
Spain 2 1%
Japan 2 1%
Denmark 1 <1%
Sweden 1 <1%
Unknown 178 94%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 50 26%
Researcher 43 23%
Student > Master 21 11%
Student > Postgraduate 16 8%
Student > Bachelor 15 8%
Other 45 24%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 55 29%
Agricultural and Biological Sciences 49 26%
Medicine and Dentistry 36 19%
Unspecified 13 7%
Pharmacology, Toxicology and Pharmaceutical Science 10 5%
Other 27 14%

Attention Score in Context

This research output has an Altmetric Attention Score of 67. 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 03 April 2019.
All research outputs
#259,986
of 13,649,352 outputs
Outputs from Cancer Cell
#214
of 2,239 outputs
Outputs of similar age
#9,011
of 359,387 outputs
Outputs of similar age from Cancer Cell
#7
of 39 outputs
Altmetric has tracked 13,649,352 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 98th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 2,239 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 23.3. This one has done particularly well, scoring higher than 90% 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 359,387 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 82% of its contemporaries.