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Background  Patient-derived tumor xenograft models have been established and increasingly used for preclinical studies of targeted therapies in recent years. However, patient-derived non-small cell lung cancer (NSCLC) xenograft mouse models are relatively few in number and are limited in their degree of genetic characterization and validation. In this study, we aimed to establish a variety of patient-derived NSCLC models and characterize these for common genetic aberrations to provide more informative models for preclinical drug efficacy testing.    Methods  NSCLC tissues from thirty-one patients were collected and implanted into immunodeficient mice. Established xenograft models were characterized for common genetic aberrations, including detection of gene mutations within  EGFR  and  KRAS,  and genetic amplification of  FGFR1  and  cMET . Finally, gefitinib anti-tumor efficacy was tested in these patient-derived NSCLC xenograft models.    Results  Ten passable patient-derived NSCLC xenograft models were established by implantation of NSCLC specimens of thirty-one patients into immunodeficient mice. Genetic aberrations were detected in six of the models, including one model with an  EGFR  activating mutation (Exon19 Del), one model with  KRAS  mutation, one model with both  KRAS  mutation and  cMET  gene amplification, and three models with  FGFR1  amplification. Anti-tumor efficacy studies using gefitinib demonstrated that the  EGFR  activating mutation model had superior sensitivity and that the  KRAS  mutation models were resistant to gefitinib. The range of gefitinib responses in the patient-derived NSCLC xenograft models were consistent with the results reported from clinical trials. Furthermore, we observed that patient-derived NSCLC models with  FGFR1  gene amplification were insensitive to gefitinib treatment.    Conclusions  Ten patient-derived NSCLC xenograft models were established containing a variety of genetic aberrations including  EGFR  activating mutation,  KRAS  mutation, and  FGFR 1 and  cMET  amplification. Gefitinib anti-tumor efficacy in these patient-derived NSCLC xenografts containing  EGFR  and  KRAS  mutation was consistent with the reported results from previous clinical trials. Thus, data from our panel of patient-derived NSCLC xenograft models confirms the utility of these models in furthering our understanding of this disease and aiding the development of personalized therapies for NSCLC patients.

journal of translational medicine

Establishment of patient-derived non-small cell lung cancer xenograft models with genetic aberrations within EGFR, KRAS and FGFR1: useful tools for preclinical studies of targeted therapies