title: Role of mesenchymal-epithelial transition amplification in resistance to anti-epidermal growth factor receptor agents.
abstract: All patients with epidermal growth factor receptor (EGFR) mutant advanced non-small cell lung cancer (NSCLC) treated with an EGFR-tyrosine kinase inhibitor (EGFR-TKI) such as gefitinib, erlotinib or afatinib will progress after a median of 9-12 months. So far, development of a secondary T790M mutation represents the most common (approximately 60%) mechanism of resistance to these drugs. The relative rarity of mesenchymal-epithelial transition (MET) amplification in NSCLC suggests that this event plays a limited role in primary resistance to EGFR-TKI. In contrast, MET gene amplification has been detected as a secondary event representing one of the most relevant mechanisms involved in the acquired resistance to EGFR-TKIs both in preclinical and clinical studies. The aim of this review is to discuss the role of MET amplification as a mechanism of resistance to anti-EGFR therapies and to review strategies which aim at overcoming this mechanism of resistance, including studies assessing drug combinations targeting both EGFR and MET pathways.
authors.affiliation: 1 Cancer Research UK Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, UK ; 2 Department of Medical Oncology, University Hospital of South Manchester NHS Foundation Trust, Manchester M23 9LT, UK ; 3 Dipartimento di internistica clinica e sperimentale "F. Magrassi e A. Lanzara", Seconda Università degli studi di Napoli, Naples, Italy ; 4 Department of Biomedical Sciences and Medicine, University of Algarve, Faro 8005-139, Portugal ; 5 Department of Medical Oncology, Portuguese Oncology Institute, Porto 4200-072, Portugal ; 6 University of Athens School of Medicine, Athens, Greece.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Califano
authors.affiliation: 1 Cancer Research UK Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, UK ; 2 Department of Medical Oncology, University Hospital of South Manchester NHS Foundation Trust, Manchester M23 9LT, UK ; 3 Dipartimento di internistica clinica e sperimentale "F. Magrassi e A. Lanzara", Seconda Università degli studi di Napoli, Naples, Italy ; 4 Department of Biomedical Sciences and Medicine, University of Algarve, Faro 8005-139, Portugal ; 5 Department of Medical Oncology, Portuguese Oncology Institute, Porto 4200-072, Portugal ; 6 University of Athens School of Medicine, Athens, Greece.
authors.forename: Floriana
authors.initials: F
authors.lastname: Morgillo
authors.affiliation: 1 Cancer Research UK Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, UK ; 2 Department of Medical Oncology, University Hospital of South Manchester NHS Foundation Trust, Manchester M23 9LT, UK ; 3 Dipartimento di internistica clinica e sperimentale "F. Magrassi e A. Lanzara", Seconda Università degli studi di Napoli, Naples, Italy ; 4 Department of Biomedical Sciences and Medicine, University of Algarve, Faro 8005-139, Portugal ; 5 Department of Medical Oncology, Portuguese Oncology Institute, Porto 4200-072, Portugal ; 6 University of Athens School of Medicine, Athens, Greece.
authors.forename: Ramon Andrade
authors.initials: RA
authors.lastname: De Mello
authors.affiliation: 1 Cancer Research UK Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, UK ; 2 Department of Medical Oncology, University Hospital of South Manchester NHS Foundation Trust, Manchester M23 9LT, UK ; 3 Dipartimento di internistica clinica e sperimentale "F. Magrassi e A. Lanzara", Seconda Università degli studi di Napoli, Naples, Italy ; 4 Department of Biomedical Sciences and Medicine, University of Algarve, Faro 8005-139, Portugal ; 5 Department of Medical Oncology, Portuguese Oncology Institute, Porto 4200-072, Portugal ; 6 University of Athens School of Medicine, Athens, Greece.
authors.forename: Giannis
authors.initials: G
authors.lastname: Mountzios
keywords: Epidermal growth factor receptor (EGFR); crizotinib; mesenchymal-epithelial transition (MET); onartuzumab; tivantinib