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The hypoxic tumor microenvironment and drug resistance against EGFR inhibitors: preclinical study in cetuximab-sensitive head and neck squamous cell carcinoma cell lines

Overview of attention for article published in BMC Research Notes, June 2015
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Title
The hypoxic tumor microenvironment and drug resistance against EGFR inhibitors: preclinical study in cetuximab-sensitive head and neck squamous cell carcinoma cell lines
Published in
BMC Research Notes, June 2015
DOI 10.1186/s13104-015-1197-6
Pubmed ID
Authors

Carolien Boeckx, Jolien Van den Bossche, Ines De Pauw, Marc Peeters, Filip Lardon, Marc Baay, An Wouters

Abstract

Increased expression of the epidermal growth factor receptor (EGFR) is observed in more than 90% of all head and neck squamous cell carcinomas (HNSCC). Therefore, EGFR has emerged as a promising therapeutic target. Nevertheless, drug resistance remains a major challenge and an important potential mechanism of drug resistance involves the hypoxic tumor microenvironment. Therefore, we investigated the cytotoxic effect of the EGFR-targeting agents cetuximab and erlotinib under normoxia versus hypoxia. Three cetuximab-sensitive HNSCC cell lines (SC263, LICR-HN2 and LICR-HN5) were treated with either cetuximab or erlotinib. Cells were incubated under normal or reduced oxygen conditions (<0.1% O2) for 24 or 72 h immediately after drug addition. Cell survival was assessed with the sulforhodamine B assay. Cetuximab and erlotinib established a dose-dependent growth inhibition under both normal and prolonged reduced oxygen conditions in all three HNSCC cell lines. However, a significantly increased sensitivity to cetuximab was observed in SC263 cells exposed to hypoxia for 72 h (p = 0.05), with IC50 values of 2.38 ± 0.59 nM, 0.64 ± 0.38 nM, and 0.10 ± 0.05 nM under normoxia, hypoxia for 24 h and hypoxia for 72 h, respectively. LICR-HN5 cells showed an increased sensitivity towards erlotinib when cells were incubated under hypoxia for 24 h (p = 0.05). Our results suggest that both EGFR-inhibitors cetuximab and erlotinib maintain their growth inhibitory effect under hypoxia. These results suggest that resistance to anti-EGFR therapy in HNSCC is probably not the result of hypoxic regions within the tumor and other mechanisms are involved.

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 22 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 22 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 7 32%
Student > Bachelor 4 18%
Researcher 3 14%
Other 2 9%
Student > Master 1 5%
Other 3 14%
Unknown 2 9%
Readers by discipline Count As %
Medicine and Dentistry 8 36%
Biochemistry, Genetics and Molecular Biology 5 23%
Pharmacology, Toxicology and Pharmaceutical Science 3 14%
Agricultural and Biological Sciences 1 5%
Immunology and Microbiology 1 5%
Other 1 5%
Unknown 3 14%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 03 June 2015.
All research outputs
#4,312,069
of 5,180,928 outputs
Outputs from BMC Research Notes
#1,323
of 1,643 outputs
Outputs of similar age
#143,245
of 175,004 outputs
Outputs of similar age from BMC Research Notes
#59
of 74 outputs
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We're also able to compare this research output to 74 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.