Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Tissue Bank, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China.
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China.
Oncol Rep. 2017 Oct;38(4):2387-2393. doi: 10.3892/or.2017.5907. Epub 2017 Aug 14.
Cetuximab has been evaluated as a first-line treatment with conflicting results. The aim of the present study was to investigate the relationship between epidermal growth factor receptor (EGFR) status, and response and survival benefit following cetuximab treatment in gastric cancer (GC). Using 20 patient-derived GC xenograft (PDX) models, the mice (10 mice/model) were randomly assigned into two groups. The control group and treatment group were treated with PBS and cetuximab, respectively. The drug response was evaluated by monitoring tumor growth. Survival benefit was evaluated by comparing the survival curves corresponding to the time for the tumors to reach 600 mm3. Our results revealed that the PDX models treated with cetuximab had better survival than that noted for the non-treated group (P<0.05). The EGFR status was measured by FISH, qPCR, RNAish and immunohistochemistry, respectively. Four cases in the treated group were identified as responsive to cetuximab. EGFR mRNA and protein overexpression were associated with the response to cetuximab (P<0.05). EGFR amplification, mRNA and protein overexpression were associated with prolonged survival in the cetuximab-treated PDX models. Moreover, in the PDX models with EGFR amplification, mRNA or protein overexpression, cetuximab treatment was associated with a better survival compared with that noted in the untreated group in the PDX models (P<0.05), while the survival was not statistically different in the other cases (P>0.05). In conclusion, cetuximab provided survival benefit in the trial. The level of EGFR amplification and overexpression significantly predicted response and survival benefit, particularly the mRNA and protein expression level. A combination of mRNA and protein expression may predict efficacy of cetuximab more efficiently.
西妥昔单抗已被评估为一线治疗药物，但结果存在争议。本研究旨在探讨表皮生长因子受体（EGFR）状态与西妥昔单抗治疗胃癌（GC）的反应和生存获益之间的关系。使用 20 个患者来源的胃癌异种移植（PDX）模型，将小鼠（每组 10 只）随机分为两组。对照组和治疗组分别用 PBS 和西妥昔单抗处理。通过监测肿瘤生长来评估药物反应。通过比较肿瘤达到 600mm3 所需时间的生存曲线来评估生存获益。我们的结果表明，接受西妥昔单抗治疗的 PDX 模型的生存获益优于未治疗组（P<0.05）。EGFR 状态分别通过 FISH、qPCR、RNAish 和免疫组织化学进行测量。在治疗组中，有 4 例被鉴定为对西妥昔单抗有反应。EGFR mRNA 和蛋白过表达与对西妥昔单抗的反应相关（P<0.05）。EGFR 扩增、mRNA 和蛋白过表达与接受西妥昔单抗治疗的 PDX 模型的生存延长相关。此外，在 EGFR 扩增、mRNA 或蛋白过表达的 PDX 模型中，与未治疗组相比，西妥昔单抗治疗与更好的生存相关（P<0.05），而在其他情况下，生存无统计学差异（P>0.05）。总之，在本试验中，西妥昔单抗提供了生存获益。EGFR 扩增和过表达水平显著预测反应和生存获益，特别是 mRNA 和蛋白表达水平。mRNA 和蛋白表达的组合可能更有效地预测西妥昔单抗的疗效。
