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01-12-2021 | NSCLC | Technical advance

Orthotopic model of lung cancer: isolation of bone micro-metastases after tumor escape from Osimertinib treatment

Authors: Ulrich Jarry, Mégane Bostoën, Raphaël Pineau, Laura Chaillot, Valentine Mennessier, Pierre Montagne, Emilie Motte, Marjorie Gournay, Arnaud Le Goff, Thierry Guillaudeux, Rémy Pedeux

Published in: BMC Cancer | Issue 1/2021

Abstract

Background

Osimertinib is a third generation tyrosine kinase inhibitor (TKI) that targets the epidermal growth factor receptor (EGFR) in lung cancer. However, although this molecule is not subject to some of the resistance mechanisms observed in response to first generation TKIs, ultimately, patients relapse because of unknown resistance mechanisms. New relevant non-small cell lung cancer (NSCLC) mice models are therefore required to allow the analysis of these resistance mechanisms and to evaluate the efficacy of new therapeutic strategies.

Methods

Briefly, PC-9 cells, previously modified for luciferase expression, were injected into the tail vein of mice. Tumor implantation and longitudinal growth, almost exclusively localized in the lung, were evaluated by bioluminescence. Once established, the tumor was treated with osimertinib until tumor escape and development of bone metastases.

Results

Micro-metastases were detected by bioluminescence and collected for further analysis.

Conclusion

We describe an orthotopic model of NSCLC protocol that led to lung primary tumor nesting and, after osimertinib treatment, by metastases dissemination, and that allow the isolation of these small osimertinib-resistant micro-metastases. This model provides new biological tools to study tumor progression from the establishment of a lung tumor to the generation of drug-resistant micro-metastases, mimicking the natural course of the disease in human NSCLC patients.

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Title: Orthotopic model of lung cancer: isolation of bone micro-metastases after tumor escape from Osimertinib treatment
Authors: Ulrich Jarry
Mégane Bostoën
Raphaël Pineau
Laura Chaillot
Valentine Mennessier
Pierre Montagne
Emilie Motte
Marjorie Gournay
Arnaud Le Goff
Thierry Guillaudeux
Rémy Pedeux
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: NSCLC
Lung Cancer
Metastasis
Lung Cancer
NSCLC
Lung Cancer
Osimertinib
Published in: BMC Cancer / Issue 1/2021
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-021-08205-9

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Abstract

Background

Methods

Results

Conclusion

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