‘Mechanisms of acquired resistance to anti growth factor receptor agents’

Different cell-signalling pathways have been successfully targeted in various hematologic and solid malignancies. Rationale and aim Non small cell lung cancer (NSCLC) is the major cause of cancer-related death worldwide (1). This is a very heterogeneous disease and this has huge implications for clinical practice. In the past years, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib, have represented the first example of molecularly targeted agents developed in the treatment of NSCLC and are, currently, useful tools in the management of patients who progressed on previous chemotherapy and especially for those harbouring EGFR activating mutations (1). Results from phase III clinical showed a great improvement in quality of life and in survival in this subset of patients (2). In spite of these positive aspects, therapy with EGFR TKIs is limited by the emergence of drug resistance. Our group recently demonstrated the importance of the acquisition of a mesenchymal phenotype in an in vitro model of NSCLC cell lines as a mechanism of acquired resistance to anti- EGFR tyrosine kinase inhibitors (3). The epithelial- mesenchymal transition (EMT) is a process characterized by a dramatic remodelling of cell cytoskeleton and by th