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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, November 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 (91st percentile)
  • Good Attention Score compared to outputs of the same age and source (79th percentile)

Mentioned by

news
1 news outlet
twitter
16 X users
patent
4 patents

Citations

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29 Dimensions

Readers on

mendeley
71 Mendeley
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Title
High-Order Drug Combinations Are Required to Effectively Kill Colorectal Cancer Cells
Published in
Cancer Research, November 2016
DOI 10.1158/0008-5472.can-15-3425
Pubmed ID
Authors

Thomas Horn, Stéphane 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

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.

X Demographics

X Demographics

The data shown below were collected from the profiles of 16 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 71 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Netherlands 1 1%
Unknown 70 99%

Demographic breakdown

Readers by professional status Count As %
Researcher 21 30%
Student > Ph. D. Student 12 17%
Student > Bachelor 5 7%
Other 5 7%
Student > Master 5 7%
Other 11 15%
Unknown 12 17%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 24 34%
Agricultural and Biological Sciences 11 15%
Medicine and Dentistry 7 10%
Pharmacology, Toxicology and Pharmaceutical Science 4 6%
Mathematics 2 3%
Other 8 11%
Unknown 15 21%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 21. 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 28 February 2023.
All research outputs
#1,689,019
of 24,394,820 outputs
Outputs from Cancer Research
#1,148
of 18,783 outputs
Outputs of similar age
#34,368
of 424,649 outputs
Outputs of similar age from Cancer Research
#31
of 144 outputs
Altmetric has tracked 24,394,820 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 18,783 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 9.2. This one has done particularly well, scoring higher than 93% 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 424,649 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 91% of its contemporaries.
We're also able to compare this research output to 144 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 79% of its contemporaries.