title: The role of cMet in non-small cell lung cancer resistant to EGFR-inhibitors: did we really find the target?
abstract: The advent of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) represented the most important innovation in NSCLC treatment over the last years. However, despite a great initial activity, secondary mutations in the same target, or different alterations in other molecular pathways, inevitably occur, leading to the emergence of acquired resistance, in median within the first year of treatment. In this scenario, the mesenchymal-epidermal transition (cMET) tyrosine kinase receptor and its natural ligand, the hepatocyte growth factor (HGF), seem to play an important role. Indeed either the overexpression or the amplification of cMET, as well as the overexpression of the HGF, have been reported in a substantial subgroup of NSCLC patients resistant to EGFR-TKIs. Several cMET-inhibitors have been developed as potential therapeutic candidates, and are currently under investigation in clinical trials. These compounds include both monoclonal antibodies and TKIs, and most of them have been investigated as dual combinations including an anti-EGFR TKI, to improve the efficacy of the available treatments, and ultimately overcome acquired resistance to EGFR-inhibitors.
authors.forename: Francesco
authors.initials: F
authors.lastname: Passiglia
authors.forename: Nele
authors.initials: N
authors.lastname: Van Der Steen
authors.forename: Luis
authors.initials: L
authors.lastname: Raez
authors.forename: Patrick
authors.initials: P
authors.lastname: Pauwels
authors.forename: Ignacio
authors.initials: I
authors.lastname: Gil-Bazo
authors.forename: Edgardo
authors.initials: E
authors.lastname: Santos
authors.forename: Daniele
authors.initials: D
authors.lastname: Santini
authors.forename: Giovanni
authors.initials: G
authors.lastname: Tesoriere
authors.forename: Antonio
authors.initials: A
authors.lastname: Russo
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bronte
authors.forename: Karen
authors.initials: K
authors.lastname: Zwaenepoel
authors.forename: Federico
authors.initials: F
authors.lastname: Cappuzzo
authors.affiliation: Phase I - Early Clinical Trials Unit, Oncology Department, University Hospital Antwerp UZA, Wilrijkstraat 10, 2650 Edegem, Belgium. christian.rolfo@uza.be.
authors.forename: Christian
authors.initials: C
authors.lastname: Rolfo
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D002986:Clinical Trials as Topic; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004359:Drug Therapy, Combination; D066246:ErbB Receptors / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met