Treatment with Anti-VEGF and anti-EGFR in a model of malignant pleural effusion: Genic evaluation

Introduction: Malignant pleural effusion treatment is limited to primary tumor and control of pleural effusion (PE). Intrapleural therapy could lead to a less permissive microenvironment for the development of malignant pleural disease. Objectives: To evaluate anti-VEGF and anti-EGFR in malignant pleural disease and to study tumor gene expression in a model of lung adenocarcinoma. Methods: Mice received intrapleural injection of lung adenocarcinoma cells (Lewis). After 3, 7, 10 and 14 days they were treated intraplerally with anti-VEGF, anti-EGFR, anti-VEGF+anti-EGFR or saline. It was evaluated survival, gene expression of Akt1, Akt2, Bcl2, Erbb2, NF-kB, Nras and PDGF, and KRAS and EGFR mutation. Results: All animals developed malignant pleural disease with PE and tumor implants. There was no difference in survival times between the animals treated or untreated. We observed tumor overexpression of AKt1, Akt2, Bcl2, Grb2, NF-kB and Nras genes compared to normal mouse lung tissue. We did not observe differences in PDGF gene. Only treatment with anti-VEGF showed decreased expression of Erbb2. A mutation was identified in exon 2 of the KRAS gene in tumor tissue. No mutation of EGFR gene was observed. Conclusions: Anti-VEGF and/or anti-EGFR intrapleural did not have a positive impact on survival. Tumors from Lewis cells show gene overexpression of proto-oncogenes, genes related to growth and signaling cell and anti-apoptosis. It was observed KRAS mutation. Anti-VEGF had a discrete action in decrease of the Errb2 expression without impact in the survival. These findings characterize the high aggressiveness of this tumor, which could have influenced the ineffective action of these therapies.