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

• Published in: PloS one 2024-06, Vol.19 (6), p.e0304914
• Main Authors: Jarry, Ulrich, Bostoen, Megane, Archambeau, Jérome, Pineau, Raphaël, Chaillot, Laura, Jouan, Florence, Solhi, Hélène, Ferrari, Hugo, Le Guevel, Rémy, Mennessier, Valentine, Lena, Hervé, Corre, Romain, Ricordel, Charles, Guillaudeux, Thierry, Pedeux, Rémy
• Format: Article
• Language: English
• Subjects: Acrylamides - pharmacology; Adenocarcinoma; Afatinib - pharmacology; Afatinib - therapeutic use; Angiogenesis; Aniline Compounds - pharmacology; Aniline Compounds - therapeutic use; Animal models; Animal welfare; Animals; Antimitotic agents; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - pharmacology; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Bevacizumab; Bevacizumab - pharmacology; Bevacizumab - therapeutic use; Biology and Life Sciences; Cancer; Cancer therapies; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Cell culture; Cell Line, Tumor; Disease Models, Animal; Drug development; Epidermal growth factor receptors; ErbB Receptors - genetics; ErbB Receptors - metabolism; Experiments; FDA approval; Female; Genetics; Growth factors; Health aspects; Humans; Indoles; Kinases; Laboratory animals; Life Sciences; Luciferase; Lung cancer; Lung cancer, Non-small cell; Lung diseases; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Medical innovations; Medicine and Health Sciences; Mice; Monoclonal antibodies; Mutation; Non-small cell lung carcinoma; Pathogens; Physical Sciences; Piperazines - administration & dosage; Piperazines - pharmacology; Piperazines - therapeutic use; Pyrimidines; Quinazolines - administration & dosage; Quinazolines - pharmacology; Quinazolines - therapeutic use; Simvastatin; Targeted cancer therapy; Tumor cell lines; Tumor cells; Tumors; Tyrosine; Vascular endothelial growth factor; Xenograft Model Antitumor Assays
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0304914

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.