Everolimus restores gefitinib sensitivity in resistant non-small cell lung cancer cell lines

Silvia La Monica , Maricla Galetti , Roberta R. Alfieri , Andrea Cavazzoni , Andrea Ardizzoni , Marcello Tiseo , Marzia Capelletti , Matteo Goldoni , Sara Tagliaferri , Antonio Mutti , Claudia Fumarola , Mara Bonelli , Daniele Generali , Pier Giorgio Petronini

The epidermal growth factor receptor (EGFR) is a validated target for therapy in non-small cell lung cancer (NSCLC). Most patients, however, either do not benefit or develop resistance to specific inhibitors of the EGFR tyrosine kinase activity, such as gefitinib or erlotinib. The mammalian target of rapamycin (mTOR) is a key intracellular kinase integrating proliferation and survival pathways and has been associated with resistance to EGFR tyrosine kinase inhibitors. In this study, we assessed the effects of combining the mTOR inhibitor everolimus (RAD001) with gefitinib on a panel of NSCLC cell lines characterized by gefitinib-resistance and able to maintain pS6K phosphorylation after gefitinib treatment.

Mots clés: Lung cancer; EGFR; Gefitinib; Everolimus

Silvia La Monica, Maricla Galetti, Roberta R. Alfieri, Andrea Cavazzoni, Andrea Ardizzoni, et al.. Everolimus restores gefitinib sensitivity in resistant non-small cell lung cancer cell lines. Biochemical Pharmacology, 2009, 78 (5), pp.460. ⟨10.1016/j.bcp.2009.04.033⟩. ⟨hal-00497268⟩