Setting up a wide panel of patient‐derived tumor xenografts of non–small cell lung cancer by improving the preanalytical steps

作者: Marius Ilie , Manoel Nunes , Lydia Blot , Véronique Hofman , Elodie Long‐Mira

DOI: 10.1002/CAM4.357

关键词: Squamous carcinomaLung cancerPTENKRASPathologyAdenocarcinomaSurvival analysisInternal medicineOncologyNeuroblastoma RAS viral oncogene homologMedicineContext (language use)

摘要: With the ongoing need to improve therapy for non–small cell lung cancer (NSCLC) there has been increasing interest in developing reliable preclinical models test novel therapeutics. Patient-derived tumor xenografts (PDX) are considered be interesting candidates. However, establishment of such model systems requires highly specialized research facilities and introduces logistic challenges. We aimed establish an extensive well-characterized panel NSCLC xenograft context a long-distance network after careful control preanalytical steps. One hundred fresh surgically resected specimens were shipped survival medium at room temperature from hospital-integrated biobank animal facilities. Within 24 h post-surgery, fragments subcutaneously xenografted into immunodeficient mice. PDX characterization was performed by histopathological, immunohistochemical, aCGH next-generation sequencing approaches. For this system, take rate 35%, with higher rates squamous carcinoma (60%) than adenocarcinoma (13%). Patients whom tumors obtained had significantly shorter disease-free (DFS) compared patients no (P = 0.039) obtained. established large high frequency mutations (29%) EGFR, KRAS, NRAS, MEK1, BRAF, PTEN, PI3KCA genes gene amplification (20%) c-MET FGFR1. This new patient-derived collection, regardless considerable time required distance between clinic facilities, recapitulated histopathology molecular diversity provides stable human research.

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