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Inhibition of EphB4–Ephrin-B2 Signaling Enhances Response to Cetuximab–Radiation Therapy in Head and Neck Cancers

Overview of attention for article published in Clinical Cancer Research, September 2018
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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 (96th percentile)
  • High Attention Score compared to outputs of the same age and source (95th percentile)

Mentioned by

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8 news outlets
blogs
1 blog
twitter
3 X users

Citations

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26 Dimensions

Readers on

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24 Mendeley
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Title
Inhibition of EphB4–Ephrin-B2 Signaling Enhances Response to Cetuximab–Radiation Therapy in Head and Neck Cancers
Published in
Clinical Cancer Research, September 2018
DOI 10.1158/1078-0432.ccr-18-0327
Pubmed ID
Authors

Shilpa Bhatia, Jaspreet Sharma, Sanjana Bukkapatnam, Ayman Oweida, Shelby Lennon, Andy Phan, Dallin Milner, Nomin Uyanga, Antonio Jimeno, David Raben, Hilary Somerset, Lynn Heasley, Sana D. Karam

Abstract

The clinical success of targeted therapies such as cetuximab and radiation (RT) is hampered by the low response rates and development of therapeutic resistance. In the current study, we investigated the involvement of EphB4-ephrin-B2 pro-tumorigenic signaling in mediating resistance to EGFR inhibition and radiation therapy in head and neck cancers. We used patient-derived xenograft (PDX) models of head and neck squamous cell carcinoma (HNSCC) and HNSCC cell lines to test our hypothesis. Tumor tissues were subjected to PhosphoRTK array, and western blotting to detect changes in EphB4-ephrin-B2 targets. mRNA sequencing and microarray data analysis was performed on PDX tumors and HNSCC cell lines respectively to determine differences in gene expression of molecules involved in tumor cell growth, proliferation, and survival pathways. Effects on cell growth were determined by MTT assay on HNSCC cells downregulated for EphB4/ephrin-B2 expression, with and without EGFR inhibitor and radiation. Our data from locally-advanced HNSCC patients treated with standard of care definitive chemo-RT show elevated EphB4 and ephrin-B2 levels after failure of treatment. We observed significant response towards cetuximab and radiation therapy following EphB4-ephrin-B2 inhibition resulting in improved survival in tumor-bearing mice. Tumor growth inhibition was accompanied by decrease in the levels of proliferation and pro-survival molecules and increased apoptosis. Our findings underscore the importance of adopting rational drug combinations to enhance therapeutic effect. Our study documenting enhanced response of HNSCC to cetuximab-RT therapy with EphB4-ephrin-B2 blockade has the potential to translate into clinic to benefit this patient population.

X Demographics

X Demographics

The data shown below were collected from the profiles of 3 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 24 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 24 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 5 21%
Student > Bachelor 3 13%
Student > Ph. D. Student 3 13%
Student > Doctoral Student 2 8%
Researcher 2 8%
Other 4 17%
Unknown 5 21%
Readers by discipline Count As %
Medicine and Dentistry 12 50%
Biochemistry, Genetics and Molecular Biology 4 17%
Pharmacology, Toxicology and Pharmaceutical Science 1 4%
Physics and Astronomy 1 4%
Chemical Engineering 1 4%
Other 0 0%
Unknown 5 21%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 68. 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 14 September 2018.
All research outputs
#542,920
of 23,088,369 outputs
Outputs from Clinical Cancer Research
#337
of 12,666 outputs
Outputs of similar age
#13,017
of 337,356 outputs
Outputs of similar age from Clinical Cancer Research
#9
of 192 outputs
Altmetric has tracked 23,088,369 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 12,666 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.9. This one has done particularly well, scoring higher than 97% 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 337,356 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 96% of its contemporaries.
We're also able to compare this research output to 192 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 95% of its contemporaries.