title: Targeting c-MET in the battle against advanced nonsmall-cell lung cancer.
abstract: OBJECTIVE
  The mesenchymal-epidermal transition (c-MET) receptor tyrosine kinase has a central role in the cancer cell's survival. MET and its ligand, hepatocyte growth factor (HGF), have recently been identified as promising targets in solid tumors, including nonsmall-cell lung cancer (NSCLC).
  
  
  RESULTS
  Aberrant MET activation can be the result of different mechanisms such as MET and HGF overexpression, MET gene amplification or mutation. Retrospective studies in NSCLC showed that MET gene copy number is a negative prognostic factor, although few data are available on the role of MET mutations. In preclinical models, cell lines with MET gene amplification are extremely sensitive to MET inhibition. Although the inner presence of gene amplification is a rare event (1-7% cases), MET amplification has emerged as one of the critical events for acquired resistance in epidermal growth factor receptor (EGFR) mutated lung adenocarcinomas refractory to EGFR-tyrosine kinase inhibitors (TKIs). In NSCLC with acquired resistance to EGFR-TKIs, MET amplification occurs in up to 20% cases and preclinical and clinical data indicated MET and EGFR co-inhibition as a potential effective strategy to overcome resistance.
  
  
  CONCLUSIONS
  MET has recently emerged as a promising target, and ongoing trials will clarify the role of anti-MET strategies in NSCLC.
authors: Istituto Toscano Tumori, Ospedale Civile, Livorno, Italy.
authors: Lorenza
authors: L
authors: Landi
authors: Gabriele
authors: G
authors: Minuti
authors: Armida
authors: A
authors: D'Incecco
authors: Federico
authors: F
authors: Cappuzzo
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D058990:Molecular Targeted Therapy; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D019859:Proto-Oncogene Proteins c-met