title: MET overexpression and gene amplification in NSCLC: a clinical perspective.
abstract: The transmembrane tyrosine kinase mesenchymal-epidermal transition (MET) receptor and its ligand, hepatocyte growth factor, also known as scatter factor, have recently been identified as novel promising targets in several human malignancies, including non-small cell lung cancer (NSCLC). Amplification, mutation, or overexpression of theMETgene can result in aberrant activation of the MET axis, leading to migration, invasion, proliferation, metastasis, and neoangiogenesis of cancer cells, suggesting that interfering with the MET/hepatocyte growth factor pathway could represent a potential antitumor strategy. While the role ofMETmutations in NSCLC is not as yet fully understood, retrospective studies have shown that an increasedMETgene copy number is a negative prognostic factor. In NSCLC, amplification of theMETgene is a relatively rare event, occurring in approximately 4% of patients not previously exposed to systemic therapies and in up to 20% of patients with acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors. In preclinical models, the presence ofMETamplification is a predictor of high sensitivity to anti-MET compounds, and several agents have entered in clinical trials for patients having advanced disease, with promising results. The aim of the present review is to summarize available data on the role of MET in NSCLC and to describe therapeutic strategies under investigation.
authors.affiliation: Medical Oncology Department, Istituto Toscano Tumori, Ospedale Civile, Livorno, Italy.
authors.forename: Lorenza
authors.initials: L
authors.lastname: Landi
authors.affiliation: Medical Oncology Department, Istituto Toscano Tumori, Ospedale Civile, Livorno, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Minuti
authors.affiliation: Medical Oncology Department, Istituto Toscano Tumori, Ospedale Civile, Livorno, Italy.
authors.forename: Armida
authors.initials: A
authors.lastname: D'Incecco
authors.affiliation: Medical Oncology Department, Istituto Toscano Tumori, Ospedale Civile, Livorno, Italy.
authors.forename: Jessica
authors.initials: J
authors.lastname: Salvini
authors.affiliation: Medical Oncology Department, Istituto Toscano Tumori, Ospedale Civile, Livorno, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Cappuzzo
keywords: epidermal growth factor receptor; hepatocyte growth factor; mesenchymal-epidermal transition; non-small cell lung cancer