Mini‐Patient‐derived Xenograft Assay Based on Microfluidic Technology Promises to be an Effective Tool for Screening Individualized Chemotherapy Regimens for Advanced Non‐Small Cell Lung Cancer

2021 ◽  
Author(s):  
Xue Wang ◽  
Yile Sun ◽  
Yunhua Xu ◽  
Danyi Wen ◽  
Na An ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Patient Derived Xenograft ◽  
Microfluidic Technology ◽  
Individualized Chemotherapy

Abstract 914: Activity of SGN-B6A in patient-derived xenograft models of non-small cell lung cancer

2021 ◽  
Author(s):  
Robert P. Lyon ◽  
John J. Gosink ◽  
Christopher J. Hale ◽  
Jackie L. Stilwell ◽  
Sean Allred ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Patient Derived Xenograft ◽  
Xenograft Models

scholarly journals Induction of Acquired Resistance towards EGFR Inhibitor Gefitinib in a Patient-Derived Xenograft Model of Non-Small Cell Lung Cancer and Subsequent Molecular Characterization

Cells ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 740 ◽  
Author(s):  
Julia Schueler ◽  
Cordula Tschuch ◽  
Kerstin Klingner ◽  
Daniel Bug ◽  
Anne-Lise Peille ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Xenograft Model ◽  
Small Cell ◽  
Small Cell Lung ◽  
Protein Ratio ◽  
Patient Derived Xenograft ◽  
Resistant Lines

In up to 30% of non-small cell lung cancer (NSCLC) patients, the oncogenic driver of tumor growth is a constitutively activated epidermal growth factor receptor (EGFR). Although these patients gain great benefit from treatment with EGFR tyrosine kinase inhibitors, the development of resistance is inevitable. To model the emergence of drug resistance, an EGFR-driven, patient-derived xenograft (PDX) NSCLC model was treated continuously with Gefitinib in vivo. Over a period of more than three months, three separate clones developed and were subsequently analyzed: Whole exome sequencing and reverse phase protein arrays (RPPAs) were performed to identify the mechanism of resistance. In total, 13 genes were identified, which were mutated in all three resistant lines. Amongst them the mutations in NOMO2, ARHGEF5 and SMTNL2 were predicted as deleterious. The 53 mutated genes specific for at least two of the resistant lines were mainly involved in cell cycle activities or the Fanconi anemia pathway. On a protein level, total EGFR, total Axl, phospho-NFκB, and phospho-Stat1 were upregulated. Stat1, Stat3, MEK1/2, and NFκB displayed enhanced activation in the resistant clones determined by the phosphorylated vs. total protein ratio. In summary, we developed an NSCLC PDX line modelling possible escape mechanism under EGFR treatment. We identified three genes that have not been described before to be involved in an acquired EGFR resistance. Further functional studies are needed to decipher the underlying pathway regulation.

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