EGFR gene status predicts response and survival benefit in a preclinical gastric cancer trial treating patient-derived xenografts with cetuximab

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 mm(3). 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.National Natural Science Foundation of China [81101879]; National Key Technology RD Program [2011ZX09307-001-05, 2014AA020603]; Beijing Municipal Science and Technology Commission [Z121100007512010]SCI(E)ARTICLE42387-23933