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High order drug combinations are required to effectively kill colorectal cancer cells

Overview of attention for article published in Cancer Research, September 2016
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (89th percentile)
  • Good Attention Score compared to outputs of the same age and source (72nd percentile)

Mentioned by

news
1 news outlet
twitter
16 tweeters

Citations

dimensions_citation
15 Dimensions

Readers on

mendeley
57 Mendeley
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Title
High order drug combinations are required to effectively kill colorectal cancer cells
Published in
Cancer Research, September 2016
DOI 10.1158/0008-5472.can-15-3425
Pubmed ID
Authors

Thomas Horn, Stephane Ferretti, Nicolas Ebel, Angela Tam, Samuel Ho, Fred Harbinski, Ali Farsidjani, Matthew Zubrowski, William R. Sellers, Robert Schlegel, Dale Porter, Erick Morris, Jens Wuerthner, Sébastien Jeay, Joel Greshock, Ensar Halilovic, Levi A. Garraway, Giordano Caponigro, Joseph Lehár, Stéphane Ferretti, T. Horn, S. Ferretti, N. Ebel, A. Tam, S. Ho, F. Harbinski, A. Farsidjani, M. Zubrowski, W. R. Sellers, R. Schlegel, D. Porter, E. Morris, J. Wuerthner, S. Jeay, J. Greshock, E. Halilovic, L. A. Garraway, G. Caponigro, J. Lehar

Abstract

Like classical chemotherapy regimens used to treat cancer, targeted therapies will also rely upon polypharmacology, but tools are still lacking to predict which combinations of molecular-targeted drugs may be most efficacious. In this study, we used image-based proliferation and apoptosis assays in colorectal cancer cell lines to systematically investigate the efficacy of combinations of two to six drugs which target critical oncogenic pathways. Drug pairs targeting key signaling pathways resulted in synergies across a broad spectrum of genetic backgrounds, but often yielded only cytostatic responses. Enhanced cytotoxicity was observed when additional processes including apoptosis and cell cycle were targeted as part of the combination. In some cases, where cell lines were resistant to paired and tripled drugs, increased expression of anti-apoptotic proteins was observed, requiring a fourth-order combination to induce cytotoxicity. Our results illustrate how high-order drug combinations are needed to kill drug-resistant cancer cells, and they also show how systematic drug combination screening together with a molecular understanding of drug responses may help define optimal cocktails to overcome aggressive cancers.

Twitter Demographics

The data shown below were collected from the profiles of 16 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 57 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 2%
Netherlands 1 2%
Unknown 55 96%

Demographic breakdown

Readers by professional status Count As %
Researcher 20 35%
Student > Ph. D. Student 9 16%
Student > Doctoral Student 4 7%
Other 4 7%
Student > Master 4 7%
Other 8 14%
Unknown 8 14%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 21 37%
Agricultural and Biological Sciences 10 18%
Medicine and Dentistry 6 11%
Chemistry 2 4%
Mathematics 2 4%
Other 5 9%
Unknown 11 19%

Attention Score in Context

This research output has an Altmetric Attention Score of 19. 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 01 October 2017.
All research outputs
#928,532
of 14,240,496 outputs
Outputs from Cancer Research
#711
of 13,520 outputs
Outputs of similar age
#26,708
of 266,615 outputs
Outputs of similar age from Cancer Research
#21
of 75 outputs
Altmetric has tracked 14,240,496 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 93rd percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 13,520 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 7.6. This one has done particularly well, scoring higher than 94% 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 266,615 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 89% of its contemporaries.
We're also able to compare this research output to 75 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 72% of its contemporaries.