Afatinib or Bevacizumab in combination with Osimertinib efficiently control tumor development in orthotopic murine models of non-small lung cancer.

Autor: Jarry U; Univ Rennes, CNRS, INSERM, BIOSIT UAR 3480, US_S 018, Oncotrial, Rennes, France.; Biotrial Pharmacology, Unité de Pharmacologie Préclinique, Rennes, France., Bostoen M; Univ Rennes, CNRS, INSERM, BIOSIT UAR 3480, US_S 018, Oncotrial, Rennes, France., Archambeau J; Univ Rennes, CNRS, INSERM, BIOSIT UAR 3480, US_S 018, Oncotrial, Rennes, France.; Univ Rennes, INSERM, OSS (Oncogenesis Stress Signaling), UMR_S 1242, CLCC Eugene Marquis, Rennes, France., Pineau R; Univ Rennes, INSERM, OSS (Oncogenesis Stress Signaling), UMR_S 1242, CLCC Eugene Marquis, Rennes, France., Chaillot L; Univ Rennes, CNRS, INSERM, BIOSIT UAR 3480, US_S 018, Oncotrial, Rennes, France.; Univ Rennes, INSERM, OSS (Oncogenesis Stress Signaling), UMR_S 1242, CLCC Eugene Marquis, Rennes, France., Jouan F; Univ Rennes, INSERM, OSS (Oncogenesis Stress Signaling), UMR_S 1242, CLCC Eugene Marquis, Rennes, France., Solhi H; Univ Rennes, CNRS, INSERM, BIOSIT UAR 3480, US_S 018, Oncotrial, Rennes, France., Ferrari H; Univ Rennes, CNRS, INSERM, BIOSIT UAR 3480, US_S 018, Oncotrial, Rennes, France., Le Guevel R; Univ Rennes, CNRS, INSERM, BIOSIT UAR 3480, US_S 018, Oncotrial, Rennes, France., Mennessier V; Biotrial Pharmacology, Unité de Pharmacologie Préclinique, Rennes, France., Lena H; Univ Rennes, INSERM, OSS (Oncogenesis Stress Signaling), UMR_S 1242, CLCC Eugene Marquis, Rennes, France.; Centre Hospitalier Universitaire de Rennes, Univ Rennes, Rennes, France., Corre R; Univ Rennes, INSERM, OSS (Oncogenesis Stress Signaling), UMR_S 1242, CLCC Eugene Marquis, Rennes, France.; Centre Hospitalier Universitaire de Rennes, Univ Rennes, Rennes, France., Ricordel C; Univ Rennes, INSERM, OSS (Oncogenesis Stress Signaling), UMR_S 1242, CLCC Eugene Marquis, Rennes, France.; Centre Hospitalier Universitaire de Rennes, Univ Rennes, Rennes, France., Guillaudeux T; Univ Rennes, CNRS, INSERM, BIOSIT UAR 3480, US_S 018, Oncotrial, Rennes, France.; Univ Rennes, INSERM, OSS (Oncogenesis Stress Signaling), UMR_S 1242, CLCC Eugene Marquis, Rennes, France., Pedeux R; Univ Rennes, CNRS, INSERM, BIOSIT UAR 3480, US_S 018, Oncotrial, Rennes, France.; Univ Rennes, INSERM, OSS (Oncogenesis Stress Signaling), UMR_S 1242, CLCC Eugene Marquis, Rennes, France.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2024 Jun 27; Vol. 19 (6), pp. e0304914. Date of Electronic Publication: 2024 Jun 27 (Print Publication: 2024).
DOI: 10.1371/journal.pone.0304914
Abstrakt: Lung cancer is one of the most common and deadliest cancers. Preclinical models are essential to study new therapies and combinations taking tumor genetics into account. We have established cell lines expressing the luciferase gene from lines with varied genetic backgrounds, commonly encountered in patients with pulmonary adenocarcinoma. We have characterized these lines by testing their response to multiple drugs. Thus, we have developed orthotopic preclinical mouse models of NSCLC with very high engraftment efficiency. These models allow the easy monitoring of tumor growth, particularly in response to treatment, and of tumor cells dissemination in the body. We show that concomitant treatment with osimertinib (3rd generation tyrosine kinase inhibitor targeting mutated EGFR) and bevacizumab (anti-angiogenic targeting VEGF) can have a beneficial therapeutic effect on EGFR-mutated tumors. We also show that the addition of afatinib to osimertinib-treated tumors in escape leads to tumor growth inhibition. No such effect is observed with selumetinib or simvastatin. These preclinical mouse models therefore make it possible to test innovative therapeutic combinations and are also a tool of choice for studying resistance mechanisms.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Jarry et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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