Weekly osimertinib dosing prevents EGFR mutant tumor cells destined to home mouse lungs.
ADAURA trial
Adjuvant EGFR-TKI treatment
Bioluminescence imaging
Orthotopic mouse lung cancer model
Tail vein injection
Journal
Translational oncology
ISSN: 1936-5233
Titre abrégé: Transl Oncol
Pays: United States
ID NLM: 101472619
Informations de publication
Date de publication:
Aug 2021
Aug 2021
Historique:
received:
22
03
2021
revised:
19
04
2021
accepted:
21
04
2021
pubmed:
17
5
2021
medline:
17
5
2021
entrez:
16
5
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33993094
pii: S1936-5233(21)00103-0
doi: 10.1016/j.tranon.2021.101111
pmc: PMC8236545
pii:
doi:
Types de publication
Journal Article
Langues
eng
Pagination
101111Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
Références
Ecancermedicalscience. 2020 Jan 29;14:1008
pubmed: 32104210
Clin Cancer Res. 2016 Oct 15;22(20):5130-5140
pubmed: 27435396
Neuro Oncol. 2011 Dec;13(12):1364-9
pubmed: 21865399
Cancer. 2020 Aug 15;126(16):3788-3799
pubmed: 32497272
Lancet. 2009 Oct 17;374(9698):1331-8
pubmed: 19767092
J Thorac Oncol. 2014 Apr;9(4):456-63
pubmed: 24736066
Acta Pharmacol Sin. 2013 Nov;34(11):1427-36
pubmed: 24096601
Cancer. 2008 Apr 1;112(7):1455-61
pubmed: 18300256
F1000Res. 2019 Feb 15;8:190
pubmed: 31448098
J Am Assoc Lab Anim Sci. 2013 Sep;52(5):584-9
pubmed: 24041215
J Clin Oncol. 2018 Apr 10;36(11):1064-1072
pubmed: 29220295
Clin Pharmacol Drug Dev. 2019 Feb;8(2):198-207
pubmed: 29683562
Oncotarget. 2017 Oct 19;8(58):98771-98781
pubmed: 29228726
N Engl J Med. 2008 Apr 17;358(16):1663-71
pubmed: 18420499
J Neurooncol. 2010 Sep;99(2):283-6
pubmed: 20146086
Drug Dev Ind Pharm. 2017 Sep;43(9):1557-1565
pubmed: 28554216
N Engl J Med. 2020 Oct 29;383(18):1711-1723
pubmed: 32955177
J Clin Oncol. 2019 Jan 10;37(2):97-104
pubmed: 30444685