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Malignant Pleural Mesothelioma (MPM) is an aggressive tumor characterized by poor prognosis and continuously increasing incidence due to widespread exposure to asbestos. Novel approaches for MPM management could take advantage of the intrapleural administration of drugs. Our group has recently developed a novel nanoplatform using gold nanoparticles (GNPs) aimed at the local treatment of lung diseases [Cova E et al. 2015]. We already proved that engineered GNPs loaded with pemetrexed and specifically decorated with the anti-CD146 expressed by MPM cells, were highly effective in inhibiting cancer cells [Stella GM et al. Eur Respir J 2015 46: OA5003]. The MAP kinase pathway is known to regulate proliferation and survival of tumor cells, including MPM [Myioshy S et al. 2012]. Clinical improvement of selumetinib slowed down due to reported adverse events [Janne PA et al, 2013]. Here, we aimed at investigating the therapeutic efficacy of selumetinib on MPM. Therefore, we preliminary tested selumetinib on two different MPM cell lines, MSTO-211H and H2452, representative of biphasic and epithelioid subtypes respectively (Fig.1). We found that selumetinib was efficacy in inhibiting MSTO-211H line as evidenced by half maximal inhibitory concentration (IC50) of 1.59 uM after 96 h incubation. However, selumetinib was almost ineffective in inhibiting H2452 cells by using the same drug concentrations suggesting a resistance to MEK inhibitors, as already observed for melanoma cell lines (Emery et al., 2009). At least in selected cases, selumetinib might be an useful drug to be loaded by functionalized targeted GNPs