Biomarker development in MET-targeted therapy

Oncotarget. 2016 Jun 14;7(24):37370-37389. doi: 10.18632/oncotarget.8276.

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.

Keywords: MET; MET-targeted therapy; amplification; biomarker; overexpression.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents / therapeutic use*
  • Benzamides
  • Biomarkers, Tumor / antagonists & inhibitors
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinogenesis / metabolism
  • Cell Movement
  • Cell Proliferation
  • Cell Transformation, Neoplastic
  • Clinical Trials as Topic
  • Gene Amplification
  • Hepatocyte Growth Factor / metabolism*
  • Humans
  • Imidazoles / therapeutic use
  • Molecular Targeted Therapy / methods
  • Mutation
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Patient Selection
  • Protein Kinase Inhibitors / therapeutic use
  • Proto-Oncogene Proteins c-met / antagonists & inhibitors
  • Proto-Oncogene Proteins c-met / genetics
  • Proto-Oncogene Proteins c-met / metabolism*
  • Pyrazines / therapeutic use
  • Signal Transduction*
  • Triazines / therapeutic use

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Benzamides
  • Biomarkers, Tumor
  • HGF protein, human
  • Imidazoles
  • Protein Kinase Inhibitors
  • Pyrazines
  • Triazines
  • 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
  • rilotumumab
  • Hepatocyte Growth Factor
  • MET protein, human
  • Proto-Oncogene Proteins c-met
  • onartuzumab
  • capmatinib