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Afatinib efficacy against squamous cell carcinoma of the head and neck cell lines in vitro and in vivo.

Young NR, Soneru C, Liu J, Grushko TA, Hardeman A, Olopade OI, Baum A, Solca F, Cohen EE - Target Oncol (2015)

Bottom Line: Two EGFR-amplified cell lines that are resistant to gefitinib are sensitive to afatinib.Cetuximab was not found to have a synergistic effect with afatinib either in vitro or in vivo.Both afatinib and cetuximab were effective in tumor xenograft model.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine and Comprehensive Cancer Center, University of Chicago, 900 E. 57th Street, Chicago, IL, 60637, USA. natyoung@bsd.uchicago.edu.

ABSTRACT
Epidermal growth factor receptor (EGFR) inhibitors have demonstrated efficacy in squamous cell carcinoma of the head and neck (SCCHN). In addition to EGFR, other ErbB family members are expressed and activated in SCCHN. Afatinib is an ErbB family blocker that has been approved for treating patients with EGFR-mutated nonsmall cell lung cancer. We sought to determine the efficacy of afatinib in preclinical models and compare this to other EGFR-targeted agents. Afatinib efficacy was characterized in a panel of ten SCCHN cell lines and found to be most effective against cell lines amplified for EGFR. Afatinib had lower IC(50) values than did gefitinib against the same panel. Two EGFR-amplified cell lines that are resistant to gefitinib are sensitive to afatinib. Cetuximab was not found to have a synergistic effect with afatinib either in vitro or in vivo. Both afatinib and cetuximab were effective in tumor xenograft model. Afatinib is an effective agent in SCCHN especially in models with EGFR amplification.

No MeSH data available.


Related in: MedlinePlus

Viablility of ten SCCHN cell lines treated with a range of concentrations of afatinib. Results from Cell Titer Blue assays
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Fig1: Viablility of ten SCCHN cell lines treated with a range of concentrations of afatinib. Results from Cell Titer Blue assays

Mentions: Cell viability of ten SCCHN cell lines grown in monolayer cultures was determined over a range of afatinib concentrations (Fig. 1) and compared to IC50 ranges of the same cell lines to gefitinib (Table 1). In order to assess whether anti-proliferative activity could be improved upon with the addition of cetuximab, viability of cell lines with high IC50 values (SCC35 and Detroit 562) was tested at several doses (Fig. 2a, b). Treatment with cetuximab alone had little effect on cell viability, even at relatively high concentrations (100 nmol/L). The combination treatment resulted in CI values above 1, thus demonstrating no evidence of a synergistic or additive effect (data not shown). Treatment with afatinib and cetuximab was tried on additional cell lines with greater sensitivity to afatinib (SQ20B and SCC61) with similar results (Fig. 2c, d).Fig. 1


Afatinib efficacy against squamous cell carcinoma of the head and neck cell lines in vitro and in vivo.

Young NR, Soneru C, Liu J, Grushko TA, Hardeman A, Olopade OI, Baum A, Solca F, Cohen EE - Target Oncol (2015)

Viablility of ten SCCHN cell lines treated with a range of concentrations of afatinib. Results from Cell Titer Blue assays
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4492891&req=5

Fig1: Viablility of ten SCCHN cell lines treated with a range of concentrations of afatinib. Results from Cell Titer Blue assays
Mentions: Cell viability of ten SCCHN cell lines grown in monolayer cultures was determined over a range of afatinib concentrations (Fig. 1) and compared to IC50 ranges of the same cell lines to gefitinib (Table 1). In order to assess whether anti-proliferative activity could be improved upon with the addition of cetuximab, viability of cell lines with high IC50 values (SCC35 and Detroit 562) was tested at several doses (Fig. 2a, b). Treatment with cetuximab alone had little effect on cell viability, even at relatively high concentrations (100 nmol/L). The combination treatment resulted in CI values above 1, thus demonstrating no evidence of a synergistic or additive effect (data not shown). Treatment with afatinib and cetuximab was tried on additional cell lines with greater sensitivity to afatinib (SQ20B and SCC61) with similar results (Fig. 2c, d).Fig. 1

Bottom Line: Two EGFR-amplified cell lines that are resistant to gefitinib are sensitive to afatinib.Cetuximab was not found to have a synergistic effect with afatinib either in vitro or in vivo.Both afatinib and cetuximab were effective in tumor xenograft model.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine and Comprehensive Cancer Center, University of Chicago, 900 E. 57th Street, Chicago, IL, 60637, USA. natyoung@bsd.uchicago.edu.

ABSTRACT
Epidermal growth factor receptor (EGFR) inhibitors have demonstrated efficacy in squamous cell carcinoma of the head and neck (SCCHN). In addition to EGFR, other ErbB family members are expressed and activated in SCCHN. Afatinib is an ErbB family blocker that has been approved for treating patients with EGFR-mutated nonsmall cell lung cancer. We sought to determine the efficacy of afatinib in preclinical models and compare this to other EGFR-targeted agents. Afatinib efficacy was characterized in a panel of ten SCCHN cell lines and found to be most effective against cell lines amplified for EGFR. Afatinib had lower IC(50) values than did gefitinib against the same panel. Two EGFR-amplified cell lines that are resistant to gefitinib are sensitive to afatinib. Cetuximab was not found to have a synergistic effect with afatinib either in vitro or in vivo. Both afatinib and cetuximab were effective in tumor xenograft model. Afatinib is an effective agent in SCCHN especially in models with EGFR amplification.

No MeSH data available.


Related in: MedlinePlus