Abstract
BackgroundRecent evidence suggests that aromatase may be involved in the pathogenesis of malignant mesothelioma. Here, we evaluated the effect of exemestane, an inhibitor of aromatase, in the treatment of mesothelioma using in vitro and in vivo preclinical models.ResultsWe show a significant reduction of cell proliferation, survival, migration and block of cells in S phase of cell cycle in mesothelioma cells upon exemestane treatment. Moreover, we find that CD44, which is involved in mesothelioma cells migration, was modulated by exemestane via cAMP and pCREB. Most importantly, in mice mesothelioma xenograft exemestane causes a significant decrease in tumor size and the association pemetrexed/exemestane is more effective than pemetrexed/cisplatin.ConclusionThe preclinical mesothelioma model suggests that exemestane might be beneficial in mesothelioma treatment.
Highlights
Recent evidence suggests that aromatase may be involved in the pathogenesis of malignant mesothelioma
Exemestane inhibits malignant pleural mesothelioma (MPM) cell growth in vitro Exemestane was used to evaluate the impact of CYP19A1 blockade in our MPM preclinical models
Upon 24 h exemestane treatment MSTO resulted in a cell cycle arrest in S-phase (Figure 1E)
Summary
Recent evidence suggests that aromatase may be involved in the pathogenesis of malignant mesothelioma. MPM is considered to be closely associated with a personal history of prolonged exposure to asbestos fibres in patients [2,3], several etiologic factors iron [4] and simian virus 40 (SV40) [5] are reported to be involved in the development of MPM. The combination of cisplatin and pemetrexed has become standard first-line therapy worldwide for patients who are not suitable for aggressive surgery, or in whom chemotherapy is recommended as part of a multimodality regimen with a mean survival of 12.1 months and 18.34 [9,10,11]. Understanding the mechanisms of the dysregulated signaling pathways allows strategies for development of targeted new therapies against this devastating disease
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