title: Targeting the MET Pathway in Gastric and Oesophageal Cancers: Refining the Optimal Approach.
abstract: Gastric and oesophageal cancers are a major cause of global cancer-related morbidity and mortality. Improvements in treatment for locoregional and metastatic gastric and oesophageal cancer have been incremental and the overall prognosis remains poor. Increasingly, molecular classification has identified recurrent, therapeutically relevant, somatic alterations in gastroesophageal malignancies. However, other than ERBB2 amplification, molecularly directed therapies have not translated to improved survival. Amplification of the receptor tyrosine kinase MET is found in about 5% of gastroesophageal cancers and represents an oncogenic driver and therapeutic target. Small series have shown activity of MET-directed tyrosine kinase inhibitors, but the clinical benefit of anti-MET antibodies has been disappointing. Here we discuss the MET pathway in gastroesophageal cancers, the clinical data for MET small molecule tyrosine kinase inhibitors, anti-MET antibodies and future clinical directions for targeting MET in gastric and oesophageal cancers. To our knowledge, this is the most comprehensive review of the clinical experience with MET-directed therapies in gastric and oesophageal cancers.
authors.affiliation: Department of Medicine, University of California Irvine, Orange, CA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Lee
authors.affiliation: Division of Hematology-Oncology, University of California Irvine, Orange, CA, USA.
authors.forename: P
authors.initials: P
authors.lastname: Tran
authors.affiliation: Division of Hematology-Oncology, University of California Irvine, Orange, CA, USA. Electronic address: sklempne@uci.edu.
authors.forename: S J
authors.initials: SJ
authors.lastname: Klempner
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods*; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met
keywords: AMG 337; MET; comprehensive genomic profiling; crizotinib; gastric cancer; oesophageal cancer