Combined Erlotinib and Cetuximab Overcome the Acquired Resistance to Gefitinib NSCLC
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摘要: 本研究通过EGFR-TKI和EGFR单克隆抗体联合应用探讨治疗EGFR突变阴性和EGFR T790M突变继发性耐药的NSCLC的疗效。方法：应用EGFR突变阴性和EGFR T790M突变继发性耐药的NSCLL细胞原代培养及药敏技术检验EGFR-TKI和EGFR单克隆抗体联合应用的疗效。结果：检测厄洛替尼和西妥昔单抗联合处理对于15例EGFR突变阴性和8例T790M突变阳性的继发性耐药的NSCLC患者原代细胞的影响，应用浓度分别为50 μg/mL西妥昔单抗和1 μM厄洛替尼作用于EGFR突变阴性的NSCLC患者原代细胞，结果显示这三组间T/C值无显著性差异（P>0.05），对于T790M突变阳性的继发性耐药的NSCLC原代细胞这三组间T/C值有显著性差异（P<0.05），联合用药组疗效明显高于单药组。结论：进一步验证了厄洛替尼和西妥昔单抗联合应用对于EGFR突变阴性的NSCLC患者无效，但对于T790M突变阳性的继发性耐药的NSCLC患者有效。
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关键词:
- 非小细胞肺癌 /
- 表皮生长因子受体酪氨酸激酶抑制剂 /
- 西妥昔单抗 /
- 表皮生长因子受体 /
- 胶原凝胶体包埋药敏检测
Abstract: To investigate if the combination of erlotinib and cetuximab can overcome drug resistance in NSCLC with the T790M mutation and enhance the effects in NSCLC without somatic mutations in their epidermal growth factor receptors ( EGFR ). Methods: The effects of the combination of erlotinib and cetuximab in the primary NSCLC cells with the T790M and L858R mutations and without somatic mutations in their EGFR were investigated. Results: The effects of the combination of cetuximab and erlotinib on the growth of EGFR TKI-resistant primary NSCLC cells with T790M mutation and without EGFR mutation suspension in vitro were investigated. The combination had a more pronounced growth inhibition than the single-agent treatment in the primary NSCLC cells with T790M mutation ( P < 0.05 ), but not in the primary NSCLC cells without EGFR mutation. Conclusion: The current date data suggest that the combination of erlotinib and cetuximab is an effective strategy for the treatment of patients with EGFR TKI-resistant NSCLC and indicate combined EGFR targeting as a clinically exploitable strategy. -
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