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Patient‐derived xenograft ( PDX ) models are a useful tool in cancer biology research. However, the number of lung cancer  PDX  is limited. In the present study, we successfully established 10  PDX , including three adenocarcinoma ( AD ), six squamous cell carcinoma ( SQ ) and one large cell carcinoma ( LA ), from 30 patients with non‐small cell lung cancer ( NSCLC ) (18  AD , 10  SQ , and 2  LA ), mainly in  SCID  hairless outbred ( SHO ) mice (Crlj: SHO ‐Prkdc scid Hr hr ). Histology of  SQ , advanced clinical stage ( III ‐ IV ), status of lymph node metastasis (N2‐3), and maximum standardized uptake value ≥10 when evaluated using a delayed  18 F‐fluoro‐2‐deoxy‐ d ‐glucose positron emission tomography ( FDG ‐ PET ) scan was associated with successful  PDX  establishment. Histological analyses showed that  PDX  had histology similar to that of patients’ surgically resected tumors ( SRT ), whereas components of the microenvironment were replaced with murine cells after several passages. Next‐generation sequencing analyses showed that after two to six passages,  PDX  preserved the majority of the somatic mutations and  mRNA  expressions of the corresponding  SRT . Two out of three  PDX  with  AD  histology had epidermal growth factor receptor (  EGFR  ) mutations (L858R or exon 19 deletion) and were sensitive to  EGFR  tyrosine kinase inhibitors ( EGFR ‐ TKI ), such as gefitinib and osimertinib. Furthermore, in one of the two  PDX  with an   EGFR   mutation, osimertinib resistance was induced that was associated with epithelial‐to‐mesenchymal transition. This study presented 10 serially transplantable  PDX  of  NSCLC  in  SHO  mice and showed the use of  PDX  with an   EGFR   mutation for analyses of  EGFR ‐ TKI  resistance.

Patient‐derived xenograft models of non‐small cell lung cancer for evaluating targeted drug sensitivity and resistance