Targeting the HGF/Met signalling pathway in cancer

Eur J Cancer. 2010 May;46(7):1260-70. doi: 10.1016/j.ejca.2010.02.028. Epub 2010 Mar 19.


Under normal conditions, hepatocyte growth factor (HGF)-induced Met tyrosine kinase (TK) activation is tightly regulated by paracrine ligand delivery, ligand activation at the target cell surface, and ligand activated receptor internalisation and degradation. Despite these controls, HGF/Met signalling contributes to oncogenesis and tumour progression in several cancers and promotes aggressive cellular invasiveness that is strongly linked to tumour metastasis. The prevalence of HGF/Met pathway activation in human malignancies has driven rapid growth in cancer drug development programmes. Pathway inhibitors can be divided broadly into biologicals and low molecular weight synthetic TK inhibitors; of these, the latter now outnumber all other inhibitor types. We review here the basic properties of HGF/Met pathway antagonists now in preclinical and clinical development as well as the latest clinical trial results. The main challenges facing the effective use of HGF/Met-targeted antagonists for cancer treatment include optimal patient selection, diagnostic and pharmacodynamic biomarker development, and the identification and testing of optimal therapy combinations. The wealth of basic information, analytical reagents and model systems available concerning HGF/Met oncogenic signalling will continue to be invaluable in meeting these challenges and moving expeditiously toward more effective disease control.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Hepatocyte Growth Factor / antagonists & inhibitors
  • Hepatocyte Growth Factor / physiology*
  • Humans
  • Neoplasms / drug therapy
  • Neoplasms / physiopathology*
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Proto-Oncogene Proteins c-met / antagonists & inhibitors
  • Proto-Oncogene Proteins c-met / physiology*
  • Receptors, Growth Factor / antagonists & inhibitors
  • Receptors, Growth Factor / physiology*


  • Antineoplastic Agents
  • HGF protein, human
  • Protein Kinase Inhibitors
  • Receptors, Growth Factor
  • Hepatocyte Growth Factor
  • MET protein, human
  • Proto-Oncogene Proteins c-met