Related Experiment Video
Updated: Nov 5, 2025
Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids
Published on: November 22, 2021
Weekly osimertinib dosing prevents EGFR mutant tumor cells destined to home mouse lungs
Ashwin Butle1, Asim Joshi2, Vanita Noronha3
1Integrated Cancer Genomics Laboratory, Advanced Centre for Treatment Research Education In Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai, Maharashtra, India 410210.
Abstract:
The recently conducted ADAURA trial concludes daily dosing of adjuvant osimertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI), improves disease-free survival with stage IB/II/IIIA EGFR -mutated non-small cell lung cancer patients in comparison to placebo. We have developed a preclinical orthotopic mouse model, using luciferase tagged lung adenocarcinoma cells harboring EGFR TKI sensitive exon 19 deletion to model and extend trial implications comparing a weekly vs daily dosing outcome of osimertinib to a first-generation TKI- erlotinib. We find that 100% of mice in both the groups receiving osimertinib daily or weekly before injection of cells show a complete absence of homing of cells in mice's lungs from day three until day 18 post-injection of cells. On the other hand, 25% and 75% of mice receiving erlotinib daily and weekly before injecting cells show homing of cells to the lungs. The tumors observed in the lungs, when dissected at day 30, confirmed the colonization of the injected cells homing to the organ. Thus, our study establishes the efficacy of pretreatment with osimertinib in reducing tumor cells' homing to mouse lungs in an in vivo mouse model.
Insights
Preclinical models show osimertinib, an EGFR tyrosine kinase inhibitor (TKI), prevents lung cancer cell homing. Both daily and weekly dosing of osimertinib demonstrated complete absence of tumor cell homing in mice.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Adjuvant osimertinib (a third-generation EGFR tyrosine kinase inhibitor) improves disease-free survival in EGFR-mutated non-small cell lung cancer (NSCLC).
- Preclinical models are crucial for extending clinical trial implications and exploring novel therapeutic strategies.
Purpose of the Study:
- To develop a preclinical orthotopic mouse model for EGFR-mutated NSCLC.
- To compare the efficacy of weekly versus daily dosing of osimertinib against a first-generation TKI, erlotinib, in preventing tumor cell homing.
Main Methods:
- Development of an orthotopic mouse model using luciferase-tagged lung adenocarcinoma cells with EGFR exon 19 deletion.
- Administration of osimertinib (daily or weekly) or erlotinib (daily or weekly) prior to tumor cell injection.
- Monitoring and confirmation of tumor cell homing and colonization in mouse lungs via bioluminescence imaging and dissection.
Main Results:
- Osimertinib, at both daily and weekly doses, completely inhibited lung cancer cell homing in 100% of mice.
- Erltinib showed limited efficacy, with 25% and 75% of mice exhibiting lung tumor cell homing with daily and weekly dosing, respectively.
- Tumor dissection at day 30 confirmed the colonization of injected cells in the lungs of mice treated with erlotinib.
Conclusions:
- Pretreatment with osimertinib is highly effective in preventing tumor cell homing to the lungs in a preclinical NSCLC model.
- Osimertinib demonstrates superior efficacy compared to erlotinib in reducing lung colonization, irrespective of dosing frequency (daily vs. weekly).
- These findings support the potential of osimertinib in preventing metastasis in EGFR-mutated NSCLC.
More Related Videos
04:25Intratibial Osteosarcoma Cell Injection to Generate Orthotopic Osteosarcoma and Lung Metastasis Mouse Models
Published on: October 28, 2021
09:38Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
Published on: August 11, 2017