title: C-MET inhibitors in the treatment of lung cancer.
abstract: Lung cancer is the most common malignant neoplasm and constitutes the most common neoplastic cause of death globally. The results of therapies employing standard chemotherapy are unsatisfactory. Currently, efforts are being made to personalize the therapy; numerous clinical studies are being conducted around the world to assess the efficacy and safety of agents directed at molecular targets. One of these molecular targets is the c-MET proto-oncogene, whose primary ligand is hepatocyte growth factor (HGF). C-MET hyperactivity has been observed in numerous neoplasms, including non-small-cell lung carcinoma. Prolonged or continuous activity of the receptor leads to excessive cell proliferation and is related to the development or progression of neoplastic disease. C-MET inhibitors can be classified into three groups: small-molecule tyrosine kinase inhibitors of the c-MET receptor (crizotinib, tivantinib, cabozantinib, foretinib), as well as monoclonal antibodies against c-MET (onartuzumab) and against the HGF ligand (ficlatuzumab, rilotumumab). The efficacy and safety of these agents is assessed both in monotherapy and in combination with other molecularly targeted agents. Furthermore, the toxicity profile of c-MET inhibitors is completely different from that of standard chemotherapy. The best understood c-MET inhibitor used in the treatment of non-small-cell lung carcinoma patients is crizotinib. It is registered for patients with the presence of ALK gene rearrangements after the failure of the first line of treatment based on platinum derivatives. The purpose of this present paper is to present clinical studies that assessed the efficacy and safety of c-MET inhibitors for the treatment of non-small-cell lung carcinoma, as well as current indications for the use of these molecules.
authors.affiliation: Department of Pulmonology, Allergology and Lung Oncology, Poznan University of Medical Sciences, Poznan, Poland, jogoz@ump.edu.pl.
authors.forename: Joanna
authors.initials: J
authors.lastname: Goździk-Spychalska
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Szyszka-Barth
authors.forename: Lukasz
authors.initials: L
authors.lastname: Spychalski
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Ramlau
authors.forename: Jerzy
authors.initials: J
authors.lastname: Wójtowicz
authors.forename: Halina
authors.initials: H
authors.lastname: Batura-Gabryel
authors.forename: Rodryg
authors.initials: R
authors.lastname: Ramlau
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D017228:Hepatocyte Growth Factor / Q000037:antagonists & inhibitors; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D058990:Molecular Targeted Therapy; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000090063:Proto-Oncogene Mas; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; C000715470:MAS1 protein, human; D047428:Protein Kinase Inhibitors; D000090063:Proto-Oncogene Mas; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met