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Synergistic activity of vorinostat combined with gefitinib but not with sorafenib in mutant KRAS human non-small cell lung cancers and hepatocarcinoma

Overview of attention for article published in OncoTargets and therapy, November 2016
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Mentioned by

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1 tweeter
facebook
1 Facebook page

Citations

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18 Dimensions

Readers on

mendeley
16 Mendeley
Title
Synergistic activity of vorinostat combined with gefitinib but not with sorafenib in mutant KRAS human non-small cell lung cancers and hepatocarcinoma
Published in
OncoTargets and therapy, November 2016
DOI 10.2147/ott.s117743
Pubmed ID
Authors

Victor Jeannot, Benoit Busser, Laetitia Vanwonterghem, Sophie Michallet, Sana Ferroudj, Murat Cokol, Jean-Luc Coll, Mehmet Ozturk, Amandine Hurbin

Abstract

Development of drug resistance limits the efficacy of targeted therapies. Alternative approaches using different combinations of therapeutic agents to inhibit several pathways could be a more effective strategy for treating cancer. The effects of the approved epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (gefitinib) or a multi-targeted kinase inhibitor (sorafenib) in combination with a histone deacetylase inhibitor (vorinostat) on cell proliferation, cell cycle distribution, apoptosis, and signaling pathway activation in human lung adenocarcinoma and hepatocarcinoma cells with wild-type EGFR and mutant KRAS were investigated. The effects of the synergistic drug combinations were also studied in human lung adenocarcinoma and hepatocarcinoma cells in vivo. The combination of gefitinib and vorinostat synergistically reduced cell growth and strongly induced apoptosis through inhibition of the insulin-like growth factor-1 receptor/protein kinase B (IGF-1R/AKT)-dependent signaling pathway. Moreover, the gefitinib and vorinostat combination strongly inhibited tumor growth in mice with lung adenocarcinoma or hepatocarcinoma tumor xenografts. In contrast, the combination of sorafenib and vorinostat did not inhibit cell proliferation compared to a single treatment and induced G2/M cell cycle arrest without apoptosis. The sorafenib and vorinostat combination sustained the IGF-1R-, AKT-, and mitogen-activated protein kinase-dependent signaling pathways. These results showed that there was synergistic cytotoxicity when vorinostat was combined with gefitinib for both lung adenocarcinoma and hepatocarcinoma with mutant KRAS in vitro and in vivo but that the combination of vorinostat with sorafenib did not show any benefit. These findings highlight the important role of the IGF-1R/AKT pathway in the resistance to targeted therapies and support the use of histone deacetylase inhibitors in combination with EGFR-tyrosine kinase inhibitors, especially for treating patients with mutant KRAS resistant to other treatments.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter 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 16 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 16 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 3 19%
Student > Ph. D. Student 3 19%
Other 2 13%
Researcher 2 13%
Student > Doctoral Student 1 6%
Other 2 13%
Unknown 3 19%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 6 38%
Medicine and Dentistry 3 19%
Agricultural and Biological Sciences 2 13%
Chemistry 1 6%
Engineering 1 6%
Other 0 0%
Unknown 3 19%

Attention Score in Context

This research output has an Altmetric Attention Score of 2. 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 22 November 2016.
All research outputs
#4,419,950
of 8,670,160 outputs
Outputs from OncoTargets and therapy
#264
of 1,092 outputs
Outputs of similar age
#149,424
of 296,426 outputs
Outputs of similar age from OncoTargets and therapy
#20
of 146 outputs
Altmetric has tracked 8,670,160 research outputs across all sources so far. This one is in the 46th percentile – i.e., 46% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,092 research outputs from this source. They receive a mean Attention Score of 2.1. This one has gotten more attention than average, scoring higher than 69% 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 296,426 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 46th percentile – i.e., 46% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 146 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 78% of its contemporaries.