Young Natalie R, Soneru Christian, Liu Jing, Grushko Tatyana A, Hardeman Ashley, Olopade Olufunmilayo I, Baum Anke, Solca Flavio, Cohen Ezra E W
Department of Medicine and Comprehensive Cancer Center, University of Chicago, 900 E. 57th Street, Chicago, IL, 60637, USA.
Department of Pediatrics, University of Texas-Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX, 75390, USA.
Target Oncol. 2015 Dec;10(4):501-8. doi: 10.1007/s11523-014-0353-6. Epub 2015 Jan 6.
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.
表皮生长因子受体（EGFR）抑制剂已在头颈部鳞状细胞癌（SCCHN）中显示出疗效。除EGFR外，其他ErbB家族成员也在SCCHN中表达并被激活。阿法替尼是一种ErbB家族阻滞剂，已被批准用于治疗EGFR突变的非小细胞肺癌患者。我们试图确定阿法替尼在临床前模型中的疗效，并将其与其他EGFR靶向药物进行比较。在一组10种SCCHN细胞系中对阿法替尼的疗效进行了表征，发现其对EGFR扩增的细胞系最有效。在同一组细胞系中，阿法替尼的半数抑制浓度（IC50）值低于吉非替尼。两种对吉非替尼耐药的EGFR扩增细胞系对阿法替尼敏感。无论是在体外还是体内，均未发现西妥昔单抗与阿法替尼有协同作用。阿法替尼和西妥昔单抗在肿瘤异种移植模型中均有效。阿法替尼在SCCHN中是一种有效的药物，尤其是在EGFR扩增的模型中。
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