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Concurrent Inhibition of ERK and Farnesyltransferase Suppresses the Growth of HRAS Mutant Head and Neck Squamous Cell Carcinoma

Overview of attention for article published in Molecular Cancer Therapeutics, February 2022
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About this Attention Score

  • Above-average Attention Score compared to outputs of the same age (63rd percentile)
  • Above-average Attention Score compared to outputs of the same age and source (62nd percentile)

Mentioned by

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9 tweeters

Citations

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2 Dimensions

Readers on

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10 Mendeley
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Title
Concurrent Inhibition of ERK and Farnesyltransferase Suppresses the Growth of HRAS Mutant Head and Neck Squamous Cell Carcinoma
Published in
Molecular Cancer Therapeutics, February 2022
DOI 10.1158/1535-7163.mct-21-0142
Pubmed ID
Authors

Sehrish Javaid, Antje Schaefer, Craig M. Goodwin, Victoria V. Nguyen, Frances L. Massey, Mariaelena Pierobon, Da'Jhnae Gambrell-Sanders, Andrew M. Waters, Kathryn N. Lambert, J. Nathaniel Diehl, G. Aaron Hobbs, Kris C. Wood, Emanuel F. Petricoin, Channing J. Der, Adrienne D. Cox

Abstract

Human papilloma virus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) is a common cancer worldwide with an unmet need for more effective, less toxic treatments. Currently, both the disease and the treatment of HNSCC cause significant mortality and morbidity. Targeted therapies hold new promise for HPV-negative patients whose tumors harbor oncogenic HRAS mutations. Recent promising clinical results have renewed interest in the development of farnesyltransferase inhibitors (FTIs) as a therapeutic strategy for HRAS-mutant cancers. With the advent of clinical evaluation of the FTI tipifarnib for the treatment of HRAS-mutant HNSCC, we investigated the activity of tipifarnib and inhibitors of HRAS effector signaling in HRAS-mutant HNSCC cell lines. First, we validated that HRAS is a cancer driver in HRAS-mutant HNSCC lines. Second, we showed that treatment with the FTI tipifarnib largely phenocopied HRAS silencing, supporting HRAS as a key target of FTI anti-tumor activity. Third, we performed reverse phase protein array (RPPA) analyses to profile FTI treatment-induced changes in global signaling, and conducted CRISPR/Cas9 genetic loss of function screens to identify previously unreported genes and pathways that modulate sensitivity to tipifarnib. Fourth, we determined that concurrent inhibition of HRAS effector signaling (ERK, PI3K, mTORC1) increased sensitivity to tipifarnib treatment, in part by overcoming tipifarnib-induced compensatory signaling. We also determined that ERK inhibition could block tipifarnib-induced epithelial-to-mesenchymal transition (EMT), providing a potential basis for the effectiveness of this combination. Our results support future investigations of these and other combination treatments for HRAS mutant HNSCC.

Twitter Demographics

The data shown below were collected from the profiles of 9 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 10 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 10 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 3 30%
Student > Ph. D. Student 2 20%
Student > Postgraduate 1 10%
Unknown 4 40%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 2 20%
Medicine and Dentistry 2 20%
Agricultural and Biological Sciences 1 10%
Unknown 5 50%

Attention Score in Context

This research output has an Altmetric Attention Score of 4. 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 27 May 2022.
All research outputs
#6,658,465
of 21,422,252 outputs
Outputs from Molecular Cancer Therapeutics
#1,480
of 3,702 outputs
Outputs of similar age
#119,665
of 336,612 outputs
Outputs of similar age from Molecular Cancer Therapeutics
#14
of 37 outputs
Altmetric has tracked 21,422,252 research outputs across all sources so far. This one has received more attention than most of these and is in the 68th percentile.
So far Altmetric has tracked 3,702 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 7.9. This one has gotten more attention than average, scoring higher than 59% 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 336,612 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 63% of its contemporaries.
We're also able to compare this research output to 37 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 62% of its contemporaries.