Limits...
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

EGFR and HER2 FISH. Images of metaphase and interphase nuclei after FISH are presented. The EGFR and HER2 genes are localized by red fluorescent signals, and chromosome 7 and 17 centromeres (CEP7 and CEP17) are localized by green fluorescent signals. The cells were counterstained with DAPI (blue). EGFR/CEP7 staining of a SCC58 and b SCC28 cells. HER2/CEP17 staining of c SCC25, d HN5, e SCC58, f SQ20B, g SCC61, and h SCC28
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4492891&req=5

Fig7: EGFR and HER2 FISH. Images of metaphase and interphase nuclei after FISH are presented. The EGFR and HER2 genes are localized by red fluorescent signals, and chromosome 7 and 17 centromeres (CEP7 and CEP17) are localized by green fluorescent signals. The cells were counterstained with DAPI (blue). EGFR/CEP7 staining of a SCC58 and b SCC28 cells. HER2/CEP17 staining of c SCC25, d HN5, e SCC58, f SQ20B, g SCC61, and h SCC28

Mentions: Four of our SSCHN cell lines were EGFR amplified by FISH (Table 2, Fig. 7a and [26]). SCC58, HN5, and SQ20B exhibit high amplification (EGFR/CEP7 ratio >7), and SCC25 exhibits low amplification (EGFR/CEP7 ratio ~2). These same four lines show a gain of EGFR mRNA copies normalized to 18 s mRNA while the remaining cell lines do not (Table 2 and [26]). SCC28 cells do not show EGFR amplification (Table 2) but have high EGFR gene polysomy (Fig. 7b).Table 2


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)

EGFR and HER2 FISH. Images of metaphase and interphase nuclei after FISH are presented. The EGFR and HER2 genes are localized by red fluorescent signals, and chromosome 7 and 17 centromeres (CEP7 and CEP17) are localized by green fluorescent signals. The cells were counterstained with DAPI (blue). EGFR/CEP7 staining of a SCC58 and b SCC28 cells. HER2/CEP17 staining of c SCC25, d HN5, e SCC58, f SQ20B, g SCC61, and h SCC28
© Copyright Policy
Related In: Results  -  Collection

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

Fig7: EGFR and HER2 FISH. Images of metaphase and interphase nuclei after FISH are presented. The EGFR and HER2 genes are localized by red fluorescent signals, and chromosome 7 and 17 centromeres (CEP7 and CEP17) are localized by green fluorescent signals. The cells were counterstained with DAPI (blue). EGFR/CEP7 staining of a SCC58 and b SCC28 cells. HER2/CEP17 staining of c SCC25, d HN5, e SCC58, f SQ20B, g SCC61, and h SCC28
Mentions: Four of our SSCHN cell lines were EGFR amplified by FISH (Table 2, Fig. 7a and [26]). SCC58, HN5, and SQ20B exhibit high amplification (EGFR/CEP7 ratio >7), and SCC25 exhibits low amplification (EGFR/CEP7 ratio ~2). These same four lines show a gain of EGFR mRNA copies normalized to 18 s mRNA while the remaining cell lines do not (Table 2 and [26]). SCC28 cells do not show EGFR amplification (Table 2) but have high EGFR gene polysomy (Fig. 7b).Table 2

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