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ATM deficiency generating genomic instability sensitizes pancreatic ductal adenocarcinoma cells to therapy-induced DNA damage

Overview of attention for article published in Cancer Research, August 2017
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  • Above-average Attention Score compared to outputs of the same age (59th percentile)
  • Average Attention Score compared to outputs of the same age and source

Mentioned by

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7 tweeters

Citations

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40 Dimensions

Readers on

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52 Mendeley
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Title
ATM deficiency generating genomic instability sensitizes pancreatic ductal adenocarcinoma cells to therapy-induced DNA damage
Published in
Cancer Research, August 2017
DOI 10.1158/0008-5472.can-17-0634
Pubmed ID
Authors

Lukas Perkhofer, Anna Schmitt, Maria Carolina Romero Carrasco, Michaela Ihle, Stephanie Hampp, Dietrich Alexander Ruess, Elisabeth Hessmann, Ronan Russell, André Lechel, Ninel Azoitei, Qiong Lin, Stefan Liebau, Meike Hohwieler, Hanibal Bohnenberger, Marina Lesina, Hana Algül, Laura Gieldon, Evelin Schröck, Jochen Gaedcke, Martin Wagner, Lisa Wiesmüller, Bence Sipos, Thomas Seufferlein, Hans Christian Reinhardt, Pierre-Olivier Frappart, Alexander Kleger, Perkhofer, Lukas, Schmitt, Anna, Romero Carrasco, Maria Carolina, Ihle, Michaela, Hampp, Stephanie, Ruess, Dietrich Alexander, Hessmann, Elisabeth, Russell, Ronan, Lechel, André, Azoitei, Ninel, Lin, Qiong, Liebau, Stefan, Hohwieler, Meike, Bohnenberger, Hanibal, Lesina, Marina, Algül, Hana, Gieldon, Laura, Schröck, Evelin, Gaedcke, Jochen, Wagner, Martin, Wiesmüller, Lisa, Sipos, Bence, Seufferlein, Thomas, Reinhardt, Hans Christian, Frappart, Pierre-Olivier, Kleger, Alexander

Abstract

Pancreatic adenocarcinomas (PDAC) harbour recurrent functional mutations of the master DNA damage response kinase ATM which has been shown to accelerate tumorigenesis and epithelial-mesenchymal transition. To study how ATM deficiency affects genome integrity in this setting, we evaluated the molecular and functional effects of conditional Atm deletion in a mouse model of PDAC. ATM deficiency was associated with increased mitotic defects, recurrent genomic rearrangements and deregulated DNA integrity checkpoints, reminiscent of human PDAC. We hypothesized that altered genome integrity might allow synthetic lethality-based options for targeted therapeutic intervention. Supporting this possibility, we found that the PARP inhibitor olaparib or ATR inhibitors reduced the viability of PDAC cells in vitro and in vivo associated with a genotype-selective increase in apoptosis. Overall, our results offered a preclinical mechanistic rationale for the use of PARP and ATR inhibitors to improve treatment of ATM-mutant PDAC.

Twitter Demographics

The data shown below were collected from the profiles of 7 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 52 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 52 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 11 21%
Student > Master 9 17%
Student > Ph. D. Student 6 12%
Other 5 10%
Student > Bachelor 4 8%
Other 8 15%
Unknown 9 17%
Readers by discipline Count As %
Medicine and Dentistry 14 27%
Biochemistry, Genetics and Molecular Biology 14 27%
Agricultural and Biological Sciences 8 15%
Pharmacology, Toxicology and Pharmaceutical Science 1 2%
Immunology and Microbiology 1 2%
Other 1 2%
Unknown 13 25%

Attention Score in Context

This research output has an Altmetric Attention Score of 3. 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 16 October 2017.
All research outputs
#7,811,422
of 15,056,344 outputs
Outputs from Cancer Research
#9,736
of 14,274 outputs
Outputs of similar age
#107,468
of 271,089 outputs
Outputs of similar age from Cancer Research
#164
of 331 outputs
Altmetric has tracked 15,056,344 research outputs across all sources so far. This one is in the 47th percentile – i.e., 47% of other outputs scored the same or lower than it.
So far Altmetric has tracked 14,274 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 7.7. This one is in the 31st percentile – i.e., 31% 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 271,089 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 59% of its contemporaries.
We're also able to compare this research output to 331 others from the same source and published within six weeks on either side of this one. This one is in the 49th percentile – i.e., 49% of its contemporaries scored the same or lower than it.