title: Biomarker development in MET-targeted therapy.
abstract: Activation of the MET receptor tyrosine kinase by its ligand, hepatocyte growth factor (HGF), has been implicated in a variety of cellular processes, including cell proliferation, survival, migration, motility and invasion, all of which may be enhanced in human cancers. Aberrantly activated MET/HGF signaling correlates with tumorigenesis and metastasis, and is regarded as a robust target for the development of novel anti-cancer treatments. Various clinical trials were conducted to evaluate the safety and efficacy of selective HGF/MET inhibitors in cancer patients. There is currently no optimal or standardized method for accurate and reliable assessment of MET levels, or other biomarkers that are predictive of the patient response to MET-targeted therapeutics. In this review, we discuss the importance of accurate HGF/MET signal detection as a predictive biomarker to guide patient selection for clinical trials of MET-targeted therapies in human cancers.
authors.affiliation: Amgen Biopharmaceutical Research and Development (Shanghai) Co., Ltd, Shanghai, China.
authors.forename: Yanni
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Amgen Biopharmaceutical Research and Development (Shanghai) Co., Ltd, Shanghai, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Du
authors.affiliation: Amgen Biopharmaceutical Research and Development (Shanghai) Co., Ltd, Shanghai, China.
authors.forename: Mingqiang
authors.initials: M
authors.lastname: Zhang
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D063646:Carcinogenesis / Q000378:metabolism; D002465:Cell Movement; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D002986:Clinical Trials as Topic; D005784:Gene Amplification; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D058990:Molecular Targeted Therapy / Q000379:methods; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018579:Patient Selection; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011719:Pyrazines / Q000627:therapeutic use; D015398:Signal Transduction; D014227:Triazines / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D001549:Benzamides; D014408:Biomarkers, Tumor; C066855:HGF protein, human; D007093:Imidazoles; D047428:Protein Kinase Inhibitors; D011719:Pyrazines; D014227:Triazines; C000593259:1-(1-(imidazo(1,2-a)pyridin-6-yl)ethyl)-6-(1-methyl-1H-pyrazol-4-yl)-1H-(1,2,3)triazolo(4,5-b)pyrazine; C524459:rilotumumab; D017228:Hepatocyte Growth Factor; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met; C584058:onartuzumab; C000613976:capmatinib
keywords: MET; MET-targeted therapy; amplification; biomarker; overexpression